Dermatological application with solidified fat compositions

ABSTRACT

A pharmaceutical or cosmetic carrier or composition for topical application characterized by rheological properties which render the carrier or composition semi-solid at rest and a liquid upon application of shear forces thereto. The composition or carrier are prepared by mixing 1-25 percent of a solidifying agent and 75-99 percent of a hydrophobic solvent, by weight, wherein at least one of them has therapeutic or cosmetic benefits, in the presence or absence of a biologically active substance.

[0001] This is a continuation-in-part of U.S. Provisional PatentApplication No. 60/216,162, filed Jul. 3, 2000.

FIELD AND BACKGROUND OF THE INVENTION

[0002] The present invention relates to a pharmaceutical or cosmeticcarrier or composition for topical application onto skin and/or mucosalmembranes (e.g., the mucosa of the nose, mouth, eye, ear, vagina orrectum). More particularly, the present invention relates to (i) acosmetic or pharmaceutical carrier or composition characterized byrheological properties which render the carrier or compositionsemi-solid at rest and liquid upon application of shear forces (e.g.,spread forces) thereto; (ii) methods of preparing same; and (iii)methods of utilizing same for treating a variety of skin or mucosalmembrane diseases or disorders.

[0003] Most of the skin or mucosal membrane diseases or disorders arethe result of inflammation caused by inflammatory agents, such as, butnot limited to, bacterial, fungal, viral, parasitic, autoimmune,allergic, hormonal and/or malignant inflammatory agents. The most commonskin diseases or disorders include eczema, psoriasis and dermatitis,including contact dermatitis, atopic dermatitis and seborrheicdermatitis.

[0004] Eczema and dermatitis result from inflammatory processes thatinvolve the upper dermis and epidermis of the skin. When eczemadevelops, the keratinocytes in the epidermis distend from one anotherand fluid is accumulated there amongst in a process known as spongiosis.

[0005] In chronic forms of eczema or dermatitis the main change includethickening of the epidermis, which leads to itching, roughening andscaling of the skin surface. The loss of water from the skin leads toinflammation of the horny layer, which later result in cracked and soreskin.

[0006] Dermatitis is further classified into contact dermatitis(allergic or non allergic), atopic dermatitis and seborrheic dermatitis.

[0007] Non allergic contact dermatitis occurs in response to skinirritants, such as acids, alkalis, oils, detergents and solvents.

[0008] Allergic contact dermatitis occurs as a result of sensitizationto repeated exposure to an antigen. Allergic contact dermatitis appearsin skin areas that were in direct contact with the antigen.

[0009] Atopic dermatitis, which affects mainly infants, is characterizedby sensitization of the skin to a wide range of common antigens.

[0010] Seborrheic dermatitis affects the scalp and other hairy areas,the face, and flexural areas and results from yeast or bacteria inducedinflammation. Most people suffer from dandruff which is a mild form ofseborrheic dermatitis.

[0011] Psoriasis is a dominant autosomal inherited inflammatory diseasecharacterized by enhanced proliferation of keratinocytes whichproliferation leads to formation of scaly plaques on, for example, theknees, elbows, buttocks, and which are esthetically unpleasant and causediscomfort to the affected subject.

[0012] Skin diseases or disorders are usually treated by creams, gels orointments containing antifungal agents, steroidal agents and/orantibacterial agents. In many instances such creams, gels and ointmentsare difficult to spread, result in a greasy and sticky appearance andare usually not appealing for use.

[0013] Genital infections are caused by fungal, viral and microbialagents. Genitals infections are treated either systematically, or by theuse of creams, ointments or pessaries, which usually leak or otherwisefail to spread well and lead to ineffective therapeutic concentration ofthe therapeutically active agent(s) therein.

[0014] Genital herpes infections are widespread from the 70's and apartfrom the discomfort they inflict, genital herpes infections may, in somecases, develop into severe disease. Presently, there is no effectivemedication for genital herpes.

[0015] Trichomoniasis is an infection of the urogenital tract caused dueto infection by the protozoan Trichomonas vaginalis. Trichomoniasis isassociated with uncomfort itching and vaginal excretion in women.

[0016] Candidiasis is caused by Candida albicans and results in itchingin the genital area and white discharge therefrom.

[0017] Mucosal membrane inflammations can affect other organs such asfor example, the eye. Conjuctivitis, caused by different types ofbacteria, such as, but not limited to, Staphylococcus aureus,Streptococcus pneumoniae or Haemophilus influenzae, is generally treatedwith antibiotic ointments, e.g., bacitracin 500 U/g or gentamicin 0.3percent ophthalmic ointment instilled into the affected eye. Thecompliance to these ointments is usually poor due to the sticky feelingthey exert.

[0018] As is evident from the above descriptions, one of the importantroutes of administration of a drug for treating a skin or mucosalmembrane is by topical application of a drug onto the skin or mucosalmembrane. This method is useful for local treatment but it is alsopossible to apply pessaries via the rectum as an efficient deliverymethod of systemic agents that are not degraded in the intestine.

[0019] Many pharmaceutical carriers are presently known, most of themhave disadvantages when topically applied onto the skin or mucosalmembranes. For example, when ointments containing petroleum as a carrierare applied onto a skin wound, metabolic products and excreta from thewound cannot be easily removed therefrom because of the difficulty ofpassing through the hydrophobic petroleum barrier. In addition, theactive drug ingredient, which is dissolved or dispersed in the petroleumcarrier, is not efficiently absorbed into the wound tissue, thus, theefficacy of the drug is affected. Another example is ophthalmologicointments, which are applied into the eye, and make the eye area stickyand uncomfortable. Moreover, in physiological aspect, petroleumrestricts respiration of a wound tissue and is disturbing to the normalrespiration of the skin.

[0020] Many groups of drugs including, for example, antibiotic,antifungal, antiinflammatory, anesthetic, analgesic, antiallergic,corticosteroid, retinoid and antiproliferative medications arepreferably administered typically using a hydrophobic carrier such aspetroleum. However, due to the undesirable consistency of petroleum andsimilar hydrophobic carriers, their topical use is limited. Anadditional disadvantage of petroleum-carrier including products relatesto the greasy feeling following their topical application to the skin ormucosal membranes.

[0021] Besides petroleum, other hydrophobic pharmaceutical carriers areknown, including liquid paraffin, lanolin, beeswax, vegetable oil,glycerin monostearate, higher alcohols, polyethylene glycol and someemulsifying agents. All of these agents either suffer the limitationsdescribed hereinabove with respect to petroleum or have undesirable(fast) flow properties.

[0022] Several hydrophobic liquids, e.g., mono- and poly-unsaturatedoils from vegetable and marine sources, silicone oils, mineral oils, andliquid hydrophobic plant-derived oils are known for their therapeuticeffects when applied topically. Oils may also contain essentialnutritional constituents, such as oil-soluble vitamins (e.g., vitamin Aand vitamin E), minerals and other therapeutically effectiveconstituents. Administration of such therapeutic oils in a liquid formdoes not exert sufficient amounts of the therapeutic agents, because ofthe oil flow-spread properties. Other examples of therapeutic oilsinclude mineral and silicone oils, which are useful for the treatment ofskin dehydration and other medical diseases or disorders. These oils arealso liquid at ambient temperature.

[0023] There is thus a widely recognized need for, and it would behighly advantageous to have a new pharmaceutical or cosmetic compositionor carrier which is semi-solid at rest and which liquefies uponapplication of shear forces thereto, because such a pharmaceutical orcosmetic composition or carrier can be topically applied as a semi-solidonto an affected area and then turn into a liquid upon spreading,resulting in faster absorption and less greasiness and stickiness.

SUMMARY OF THE INVENTION

[0024] According to one aspect of the present invention there isprovided a pharmaceutical or cosmetic carrier comprising, by weight,1-25 percent of a solidifying agent and 75-99 percent of a hydrophobicsolvent.

[0025] According to another aspect of the present invention there isprovided a method of preparing a pharmaceutical or cosmetic carrier, themethod comprising the steps of mixing a hydrophobic solvent and asolidifying agent at a temperature above a melting temperature of thesolidifying agent so as to obtain a mixture containing 75-99 percent ofthe hydrophobic solvent by weight and 1-25 percent of the solidifyingagent by weight; and cooling the mixture.

[0026] According to yet another aspect of the present invention there isprovided a pharmaceutical or cosmetic composition comprising, by weight,1-25 percent of a solidifying agent and 75-99 percent of a hydrophobicsolvent, wherein at least one of the solidifying agent and thehydrophobic solvent has a therapeutic or cosmetic beneficial effect.

[0027] According to still another aspect of the present invention thereis provided a pharmaceutical or cosmetic composition comprising (a) apharmaceutical or cosmetic carrier containing, by weight, 1-25 percentof a solidifying agent and 75-99 percent of a hydrophobic solvent; and(b) a therapeutically or cosmetically effective amount of a biologicallyactive substance.

[0028] According to an additional aspect of the present invention thereis provided a method of preparing a pharmaceutical or cosmeticcomposition, the method comprising the steps of mixing a hydrophobicsolvent and a solidifying agent at a temperature above a meltingtemperature of the solidifying agent so as to obtain a pharmaceutical orcosmetic mixture containing 75-99 percent of the hydrophobic solvent byweight and 1-25 percent of the solidifying agent by weight and furthermixing into the mixture a therapeutically or cosmetically effectiveamount of a biologically active substance.

[0029] According to yet an additional aspect of the present inventionthere is provided a method of treating a disease or disorder of a skinor a mucosal membrane, the method comprising the step of topicallyadministrating to the skin or the mucosal membrane a pharmaceutical orcosmetic composition containing, by weight, 1-25 percent of asolidifying agent and 75-99 percent of a hydrophobic solvent, wherein atleast one of the solidifying agent and the hydrophobic solvent has atherapeutic or cosmetic beneficial effect

[0030] According to a further aspect of the present invention there isprovided a method of treating a disease or disorder of a skin or amucosal membrane, the method comprising the step of topicallyadministrating to the skin or the mucosal membrane a pharmaceutical orcosmetic composition containing (a) a pharmaceutical or cosmetic carriercontaining, by weight, 1-25 percent of a solidifying agent and 75-99percent of a hydrophobic solvent; and (b) a therapeutically orcosmetically effective amount of a biologically active substance.

[0031] According to further features in preferred embodiments of theinvention described below, the solidifying agent is selected from thegroup consisting of at least one long chain fatty alcohol having atleast 15 carbon atoms in its carbon backbone and at least one fattyacid, having at least 18carbon atoms in its carbon backbone.

[0032] According to still further features in the described preferredembodiments the solidifying agent includes a substance selected suchthat under ambient conditions, the carrier is semi-solid at rest andliquefies upon application of shear forces thereto.

[0033] According to still further features in the described preferredembodiments the hydrophobic solvent is selected from the groupconsisting of at least one marine animal derived oil, at least oneterrestrial animal derived oil, at least one mineral oil, at least onesilicone oil and at least one plant-derived oil.

[0034] According to still further features in the described preferredembodiments the hydrophobic solvent includes an oil selected from thegroup consisting of olive oil, soybean oil, canola oil, rapeseed oil,cottonseed oil, coconut oil, palm oil, sesame oil, sunflower oil,safflower oil, rice bran oil, borage seed oil, syzigium aromaticum oil,hempseed oil, herring oil, cod-liver oil, salmon oil, corn oil, flaxseedoil, wheat germ oil, rape seed oil, evening primrose oil, rosehip oil,tea tree oil, melaleuca oil and jojova oil.

[0035] According to still further features in the described preferredembodiments the hydrophobic solvent includes an oil selected from thegroup consisting of omega-3 oil and omega-6 oil.

[0036] According to still further features in the described preferredembodiments the solidifying agent has at least one alkyl group sidechain in its carbon backbone.

[0037] According to still further features in the described preferredembodiments the carbon backbone of the fatty acid and/or the fattyalcohol has at least one hydroxyl group at position α or β.

[0038] According to still further features in the described preferredembodiments the carbon backbone of the fatty acid or the fatty alcoholhas at least one hydroxyl group at positions 8-14.

[0039] According to still further features in the described preferredembodiments the solidifying agent includes a 12-hydroxy fatty acid.

[0040] According to still further features in the described preferredembodiments at least one of the solidifying agent and the hydrophobicsolvent have a therapeutic or cosmetic beneficial effect.

[0041] According to still further features in the described preferredembodiments the skin or the mucosal membrane disease or disorderincludes inflammation caused by an inflammatory agent selected from thegroup consisting of a bacterial inflammatory agent, a fungalinflammatory agent, a viral inflammatory agent, a parasitic inflammatoryagent, an autoimmune inflammatory agent, an allergic inflammatory agent,a hormonal inflammatory agent and a malignant inflammatory agent.

[0042] According to still further features in the described preferredembodiments the skin disease or disorder is selected from the groupconsisting of psoriasis, acne, seborrhea, seborrheic dermatitis,alopecia and excessive hair growth, itching, wounds, burns, cuts,ulcers, seborrheic dermatitis of the face and trunk, seborrheicblepharitis, contact dermatitis, stasis dermatitis and exfoliativedermatitis.

[0043] According to still further features in the described preferredembodiments the statis dermatitis is selected from the group consistingof gravitational eczema, varicose eczema and the exfoliative dermatitisis erythroderma.

[0044] According to still further features in the described preferredembodiments the biologically active substance is selected from the groupconsisting of an antibiotic agent, a free radical generating agent, anantifungal agent, an antiviral agent, a non-nucleoside reversetranscriptase inhibitor, a nucleoside-analog reverse transcriptaseinhibitor, a protease inhibitor, a protease inhibitor, a non-steroidalantiinflammatory drug, an immunosuppressant, an antihistamine agent, anantiinflammatory agent, a retinoid agent, a tar agent, an antipruriticsagent and a scabicide agent.

[0045] According to still further features in the described preferredembodiments (a) the antibiotic agent is selected from the groupconsisting of chloramphenicol, tetracyclines, synthetic andsemi-synthesic penicillins, beta-lactames, quinolones, fluoroquinolnes,macrolide antibiotics, peptide antibiotics, cyclosporines, erytromycinand clinndamycin; (b) the free radical generating agent is benzoylperoxide; (c) the antifungal agent is selected from the group consistingof azoles, diazole, triazole, miconazole, fluconazole, ketoconazole,clotrimazole, itraconazole griseofulvin, ciclopirox, amorolfine,terbinafine, Amphotericin B and potassium iodide; (d) the antiviralagent is selected from the group of flucytosine (5FC), Vidarabine,acyclovir and Gancyclovir; (e) the nucleoside-analog reversetranscriptase inhibitor is selected from the group consisting ofZidovudine, Stavudine and Lamivudine; (f) the non-nucleoside reversetranscriptase inhibitor is selected from the group consisting ofNevirapine and Delavirdine; (g) the protease inhibitor is selected fromthe group consisting of Saquinavir, Ritonavir, Indinavir, Nelfinavir,Ribavirin Amantadine, Rimantadine and Interferon; (h) theimmunosuppressant is selected from the group consisting of Clobetasolproprionate, Halobetasol proprionate, Betamethasone diproprionate,Betamethasone valerate, Fluocinolone acetonide, Halcinonide,Betamethasone valerate, Fluocinolone acetonide, Hydrocortisone valerate,Triamcinolone acetonide, Hydrocortisone and hexachlorobenzene; (i) theantiinflammatory agent is a vitamin B3 derivative; (j) the retinoidagent is selected from the group consisting of isotretinoin, adapaleneand tretinoin; (k) the tar agent is selected from the group consistingof coal tar and cade oil; (l) the antihistamine agent is doxepinehydrochloride; (m) the antipruritic agent is crotampiton; and (n) thescabicide agent is selected from the group consisting of benzylbenzoate, malathion and crotamiton.

[0046] According to still further features in the described preferredembodiments the biologically active substance is effective in thetreatment of psoriasis, acne, seborrhea, seborrheic dermatitis, alopeciaand excessive hair growth, ichthyosis, wounds, burns, cuts, ulcers,psoriasis, seborrheic dermatitis of the face and trunk, seborrheicblepharitis, contact dermatitis, stasis dermatitis or exfoliativedermatitis.

[0047] According to still further features in the described preferredembodiments the statis dermatitis is selected from the group consistingof gravitational eczema; varicose eczema, whereas the exfoliativedermatitis is erythroderma.

[0048] The present invention successfully addresses the shortcomings ofthe presently known configurations by providing a biologically activecarrier or composition, which is semi solid at rest and liquefies uponapplication of shear forces thereto, which is therefore easy to spread,highly absorbable, non greasy and non-sticky and which can be used forthe treatment of a great number of diseases and syndromes affecting theskin and mucosal membranes.

BRIEF DESCRIPTION OF THE DRAWINGS

[0049] The invention is herein described, by way of example only, withreference to the accompanying drawing.

[0050]FIG. 1 is a photograph demonstrating the therapeutic effects of acorticosteroid composition prepared in accordance with the teachings ofthe present invention administered twice a day for 10 days, to apsoriasis patient. The composition was prepared as described inExample 1. The photograph clearly demonstrates a reduction in thepsoriatic plaques size following the course of treatment.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0051] The present invention is of (i) a pharmaceutical or cosmeticcarrier or composition for topical application, preferably characterizedby Theological properties which render the carrier or composition asemi-solid at rest and a liquid upon application of shear forcesthereto; (ii) methods of preparing same; and (iii) methods of utilizingsame for treating skin or mucosal membrane diseases or disorders.

[0052] The principles and operation of the present invention may bebetter understood with reference to the accompanying descriptions andexamples. Before explaining at least one embodiment of the invention indetail, it is to be understood that the invention is not limited in itsapplication to the details of composition set forth in the followingdescription or examples. The invention is capable of other embodimentsor of being practiced or carried out in various ways. Also, it is to beunderstood that the phraseology and terminology employed herein is forthe purpose of description and should not be regarded as limiting.

[0053] According to one aspect of the present invention there isprovided a pharmaceutical or cosmetic carrier comprising, by weight,1-25 percent of a solidifying agent and 75-99 percent of a hydrophobicsolvent, which solvent per se is typically liquid at ambienttemperature.

[0054] As used herein in the specification and in the claims sectionthat follows, the term “carrier” means a base which is, as is defined inthe Collins dictionary, the main ingredient of a mixture. Thus, as usedherein a “pharmaceutical carrier” is a pharmaceutical base which is usedin the preparation of pharmaceutical compositions, whereas a “cosmeticcarrier” is a cosmetic base which is used in the preparation of cosmeticcompositions.

[0055] According to another aspect of the present invention there isprovided a method of preparing a pharmaceutical or cosmetic carrier. Themethod according to this aspect of the invention is effected by mixing ahydrophobic solvent and a solidifying agent at a temperature above amelting temperature of the solidifying agent so as to obtain a mixturecontaining 75-99 percent of the hydrophobic solvent by weight and 1-25percent of the solidifying agent by weight; and cooling the mixture,e.g., to room temperature. Preferably, prior to the step of mixing, boththe hydrophobic solvent and the solidifying agent are brought to thetemperature above the melting temperature of the solidifying agent.

[0056] According to still another aspect of the present invention thereis provided a pharmaceutical or cosmetic composition comprising, byweight, 1-25 percent of a solidifying agent and 75-99 percent of ahydrophobic solvent, wherein at least one of the solidifying agentand/or the hydrophobic solvent has a therapeutic or cosmetic beneficialeffect.

[0057] According to yet another aspect of the present invention there isprovided a method of preparing a pharmaceutical or cosmetic composition.The method according to this aspect of the invention is effected bymixing a hydrophobic solvent and a solidifying agent at a temperatureabove a melting temperature of the solidifying agent so as to obtain amixture containing 75-99 percent of the hydrophobic solvent by weightand 1-25 percent of the solidifying agent by weight; and cooling themixture, e.g., to room temperature. Preferably, prior to the step ofmixing, both the hydrophobic solvent and the solidifying agent arebrought to the temperature above the melting temperature of thesolidifying agent, e.g., 60-80° C.

[0058] Thus, the present invention offers a method of treating a diseaseor disorder of a skin or a mucosal membrane, such as, but not limitedto, a mucosa of a nose, a mucosa of a mouth, a mucosa of an eye, amucosa of an ear, a mucosa of a vagina and a mucosa of a rectum. Themethod according to this aspect of the present invention is effected bytopically administrating to the skin or the mucosal membrane apharmaceutical or cosmetic composition containing, by weight, 1-25percent of a solidifying agent and 75-99 percent of a hydrophobicsolvent, wherein at least one of the solidifying agent and thehydrophobic solvent has a therapeutic or cosmetic beneficial effect.

[0059] Most preferably, the amount of the solidifying agent in apharmaceutical or cosmetic carrier according to the present invention isabout 4 percent to about 12 percent, whereas the amount of thehydrophobic solvent is about 88 percent to about 96 percent of the totalweight of the carrier. As used herein the term about refers to ±20%.

[0060] According to a preferred embodiment of the present invention, thesolidifying agent includes at least one long chain fatty alcohol havingat least 15 carbon atoms in its carbon backbone and/or at least onefatty acid, having at least 18 carbon atoms in its carbon backbone.Preferably, the solidifying agent has at least one alkyl group sidechain in its carbon backbone. Additionally or alternatively, the carbonbackbone of the fatty acid or the fatty alcohol has at least onehydroxyl group at position α and β. Still additionally or alternatively,the carbon backbone of the fatty acid or the fatty alcohol has at leastone hydroxyl group at positions 8-14. According to presently preferredembodiments of the invention, the solidifying agent preferably includesa 12-hydroxy fatty acid.

[0061] According to another preferred embodiment of the presentinvention, the solidifying agent includes a substance selected such thatambient conditions, the carrier is semi-solid at rest and liquefies uponapplication of shear forces thereto, i.e., has thixotropic properties.

[0062] As mentioned above, preferred solidifying agents, according tothe present invention, include fatty alcohols having 15 or more carbonsin their carbon chain, such as acetyl alcohol and stearyl alcohol (ormixtures thereof). Other examples of fatty alcohols include arachidylalcohol (C20), behenyl alcohol (C22), 1-triacontanol (C30), as well asalcohols with longer carbon chains (e.g., up to C50). The concentrationof the fatty alcohol, required to obtain the thixotropic properties isinversely related to the length of its carbon chains.

[0063] Fatty alcohols, derived from beeswax, comprising a mixture ofalcohols, where the majority have at least 20 carbon atoms in theircarbon chain, are especially suited as solidifying agents according tothe present invention.

[0064] Another preferred class of solidifying agents includes fattyacids having 18 or more carbons in their carbon chain, such as andstearic acid, arachidic acid (C20), behenic acid (C22), octacosanoicacid (C28), as well as fatty acids with longer carbon chains (e.g., upto C50), or mixtures thereof.

[0065] The concentration of the fatty acid required to obtain athickened carrier is inversely related to the length of its carbonchains. Stearic acid, for example, exerts a considerable thickeningeffect at about 10 percent concentration, whereas behenic acid wouldobtain the same thickening effect at a 5 percent concentration.

[0066] Optionally, the carbon atom chain of the fatty alcohol or thefatty acid may have at least one double bond.

[0067] A further class of solidifying agent according to the presentinvention comprises long chain fatty alcohols or fatty acids, whereinthe carbon atom chain is branched. In an additional preferred class ofsolidifying agents, the carbon chain of the fatty acid is substitutedwith a hydroxyl group, e.g., 12 hydroxy stearic acid.

[0068] An important property of the fatty alcohols and fatty acids usedin context of the carrier and composition of the present invention isrelated to their therapeutic properties per se. Long chain saturated andmono unsaturated fatty alcohols, e.g., stearyl alcohol, erycyl alcohol,arachidyl alcohol and docosanol have been reported to possess antiviral,antiinfective, antiproliferative and antiinflammatory properties (see,U.S. Pat. No. 4,874,794, which is incorporated herein by reference).Longer chain fatty alcohols, e.g., tetracosanol, hexacosanol,heptacosanol, octacosanol, triacontanol, etc., are also known for theirmetabolism modifying properties and tissue energizing properties. Longchain fatty acids have also been reported to possess antiinfectivecharacteristics. Thus, the pharmaceutical or cosmetic carrier of thepresent invention provides an extra therapeutic or cosmetic benefit incomparison with currently used vehicles, such as petroleum, which areinert and non-active.

[0069] According to still another preferred embodiment of the presentinvention, the hydrophobic solvent includes at least one marine animalderived oil, at least one terrestrial animal derived oil, at least onemineral oil, at least one silicone oil and/or at least one plant-derivedoil. Examples include, but are not limited to, olive oil, soybean oil,canola oil, rapeseed oil, cottonseed oil, coconut oil, palm oil, sesameoil, sunflower oil, safflower oil, rice bran oil, borage seed oil,syzigium aromaticum oil, hempseed oil, herring oil, cod-liver oil,salmon oil, corn oil, flaxseed oil, wheat germ oil, rape seed oil,evening primrose oil, rosehip oil, tea tree oil, melaleuca oil and/orjojova oil.

[0070] As used herein “tea tree oil” or “melaleuca oil” both refer todistillates of the leaves of the Australian tree, Melaleucaalternifolia. Tea tree oil is assigned the Chemical Abstract number68647-73-4 and is commercially available from a variety of sources. Teatree oil is recognized as having properties as a solvent, antiseptic,antibacterial, antifungal, and pain reliever, as well as other uses.Melaleuca oil has been used in soaps, shampoos, hand creams, toothpastes, and household cleaners, as well as for treatment of warts andoral candidiasis.

[0071] A particularly preferred class of oils to be used in context ofthe present invention include poly-unsaturated oils which containsomega-3 and omega-6 fatty acids. Thus, in a presently most preferredembodiment of the present invention the carrier contains at least 6percent omega-3 oil and/or omega-6 oil.

[0072] The above described pharmaceutical or cosmetic carrier may beused in the preparation of a pharmaceutical or cosmetic compositioncomprising (a) a pharmaceutical or cosmetic carrier containing, byweight, 1-25 percent of a solidifying agent and 75-99 percent of ahydrophobic solvent, which is typically liquid at ambient temperature;and (b) a therapeutically or cosmetically effective amount of abiologically active substance. Preferably, at least one of thesolidifying agent and the hydrophobic solvent has a therapeutic orcosmetic beneficial effect.

[0073] As used herein in the specification and in the claims sectionthat follows the phrase “biologically active substance” refers to anactive ingredient which has a therapeutic or cosmetic effect followingits administration to an organism (human or animal). The therapeutic orcosmetic effect can be curing, minimizing, preventing or ameliorating adisease or disorder, or improving the physical appearance and aesthetics(e.g., skin hydration) or may have any other therapeutic or cosmeticbeneficial effect. The biologically active substance may be, forexample, a drug, a vitamin or a vaccine. Thus, the biologically activesubstances employed in context of the present invention are generallyselected from the broad categories of medicaments, agricultural productsand cosmetic products. The biologically active substance may be a singledrug or a combination of drugs that are dissolved or spread in thecarrier of the present invention. Therefore, they are usually, yet notobligatorily, hydrophobic. The concentration of the substance isselected so as to exert its therapeutic or cosmetic effect.

[0074] According to another aspect of the invention there is provided amethod of preparing a pharmaceutical or cosmetic composition. The methodaccording to this aspect of the present invention is effected by (a)mixing a hydrophobic solvent and a solidifying agent at a temperatureabove a melting temperature of the solidifying agent so as to obtain apharmaceutical or cosmetic mixture containing 75-99 percent of thehydrophobic solvent by weight, and 1-25 percent of the solidifying agentby weight; and (b) further mixing into the carrier mixture atherapeutically or cosmetically effective amount of a biologicallyactive substance. Preferably, prior to the step of mixing, both thehydrophobic solvent and the solidifying agent are brought to thetemperature above the melting temperature of the solidifying agent,e.g., 60 -80° C.

[0075] According to a preferred embodiment of this aspect of the presentinvention the biologically active substance is an antibiotic agent,e.g., chloramphenicol, tetracyclines, synthetic and semi-synthesicpenicillins, beta-lactames, quinolones, fluoroquinolnes, macrolideantibiotics, peptide antibiotics, cyclosporines, erytromycin andclinndamycin; a free radical, e.g., benzoyl peroxide; a generatingagent; an antifungal agent, e.g., azoles, diazoles, triazoles,miconazole, fluconazole, ketoconazole, clotrimazole, itraconazolegriseofulvin, ciclopirox, amorolfine, terbinafine, Amphotericin B andpotassium iodide; an antiviral agent, e.g., flucytosine (5FC),Vidarabine, acyclovir and Gancyclovir; a non-nucleoside reversetranscriptase inhibitor, Nevirapine and Delavirdine; a nucleoside-analogreverse transcriptase inhibitor, a protease inhibitor, e.g., e.g.,Zidovudine, Stavudine and Lamivudine, a protease inhibitor, e.g.,Saquinavir, Ritonavir, Indinavir, Nelfinavir, Ribavirin Amantadine,Rimantadine and Interferon; a non-steroidal antiinflammatory drug, e.g.,Voltarene; an immuno, e.g., Clobetasol proprionate, Halobetasolproprionate, Betamethasone diproprionate, Betamethasone valerate,Fluocinolone acetonide, Halcinonide, Betamethasone valerate,Fluocinolone acetonide, Hydrocortisone valerate, Triamcinoloneacetonide, Hydrocortisone and hexachlorobenzene; an antihistamine, e.g.,doxepine hydrochloride; an antiinflammatory agent, e.g., vitamin B3 or aderivative thereof; a retinoid agent, e.g., isotretinoin, adapalene andtretinoin; a tar agent, e.g., coal tar and cade oil; an antipruriticsagent, e.g., crotampiton; or a scabicide agent, e.g., benzyl benzoate,malathion and crotamiton.

[0076] The biologically active substance is preferably selectedeffective in the treatment of a disease or disorder, such as, but notlimited to, psoriasis, acne, seborrhea, seborrheic dermatitis, alopeciaand excessive hair growth, ichthyosis, wounds, burns, cuts, ulcers,psoriasis, seborrheic dermatitis of the face and trunk, seborrheicblepharitis, contact dermatitis, stasis dermatitis (e.g., gravitationaleczema, varicose eczema) or exfoliative dermatitis (e.g., erythroderma).

[0077] Thus, the present invention offers another method of treating adisease or disorder of a skin or a mucosal membrane, such as, but notlimited to, a mucosa of a nose, a mucosa of a mouth, a mucosa of an eye,a mucosa of an ear, a mucosa of a vagina and mucosa of a rectum. Themethod is effected by topically administrating thereto a pharmaceuticalor cosmetic composition containing (a) a pharmaceutical or cosmeticcarrier containing, by weight, 1-25 percent of a solidifying agent and75-99 percent of a hydrophobic solvent, which is typically liquid atambient temperature; and (b) a therapeutically or cosmetically effectiveamount of a biologically active substance.

[0078] The pH of the composition or carrier of the present invention ispreferably maintained in the range of about pH 5.5-7.0. Acids, bases,and buffers can be used according to methods well known in the art foradjusting the pH of the carrier or composition.

[0079] Pharmaceutical compositions manufactured using the carrieraccording to the present invention are very easy to use. When applied onthe afflicted body surface of humans or animals, they are in asemi-solid state, allowing free application without spillage. Uponfurther application of a mechanical force, e.g., by rubbing thecomposition onto the body surface, it freely spreads on the surface andis rapidly absorbed. The ease of the application is demonstrated hereinin Example 3, where it was compared, in a double blind test to acommercial hydrocortisone preparation. The subjects' score regardingtheir feeling about the preparation (e.g., the greasiness, stickiness,absorption, penetration, ease of spreading and lack of shiny look) wassignificantly higher than the score for the commercial preparation.

[0080] Additional particulars concerning the use of a variety ofbiologically active substances in context of the present invention,advantages of the present invention over prior art designs and a varietyof applications of the present invention are provided hereinafter.

[0081] Treatment of Wounds:

[0082] The present invention may find special advantages in thetreatment of wounds. Skin wounds which can be treated using thecompositions of the present invention include burn wounds, sunburn,cuts, abrasions, acute and chronic wounds and the like. Treatment ofburn, ulcers, acute and chronic wounds typically is directed to keepingthe wound as clean as possible and making the patient as comfortable aspossible. It has been recognized in this respect that keeping the woundmoist is advantageous to patient comfort. While maintaining a moistenvironment will effect some cooling of the tissue, it would beadvantageous to be able to decrease the intradermal temperature of aburn wound, which would help to alter the progression of the tissuedamage due to heat within the tissues.

[0083] Accordingly, it would be advantageous to provide a method forimproved treatment of a burn wound that permits significant lowering ofthe intradermal temperature of the burn wound such that the extent ofthe burn wound may be limited. Compositions which have antimicrobialagents combined with agents that lead to cooling effect, and which aredevoid of adherence to the wound offer relief to people who aresuffering from burns or ulcers. The present invention provides aprotective moisture barrier to contribute to the sterility of thedressing and to maintain the moistness of the dressing. Sterility isenhanced by the bacteriostatic properties of the wound treatmentcomposition, as well as the shielding action of the barrier's physicalpresence. An additional barrier to bacteria and contamination is thepackaging utilized with the present invention and which is addressed inmore detail below.

[0084] The wound treatment composition of the present inventioncomprises as the hydrophobic solvent, for example without limitation,tea tree oil, melaleuca oil and other ingredients in a thixotropic gelformulation. As stated hereinabove, Tea tree oil, or Melaleucaalternifolia, is a natural plant extract. The unique wound treatmentcomposition, in addition to creating a moist, soothing environment, isalso inherently bacteriostatic. It helps leave the surface of woundsclean and odor free. The odor of chronic wounds is a major concern ofhealth care workers and caregivers. The effectiveness of Melaleuca isincreased in the presence of blood and organic material, rather thandecreased as is the case with other bacteriostatic products. Melaleucaoil is a natural oil which is considered to be safe and effective on allkinds of cuts and abrasions, surgical wounds, diabetic and mouth ulcersand foot fungi.

[0085] The application of the composition of the present invention ontocuts, wounds, burns and ulcers is beneficial both in the cure of aninfection or in the protection of the skin from infection. In all suchcases, the composition of the present invention is easy to use, beingsemi-solid when applied and becoming liquid instantly upon rubbing ontothe skin.

[0086] Suppositories:

[0087] For treatment of vaginal infections, suppositories provide aneffective mode for administration of a therapeutic agent. Althoughsuppositories have attained some success, they have some disadvantages.Most of the current commercial vaginal suppositories, either melt ordissolve in the vaginal tract into an oily or aqueous liquid. Thisresulting liquid in turn tends to leak out or is expelled out of thevaginal cavity resulting either in soiled clothing and/or inferiorefficacy. Accordingly, it is an object of the present invention toprovide an effective antifungal suppository formulation, which overcomesthe noted disadvantages associated with the prior art suppositories.

[0088] The suppository formulation of the invention is useful intreating vaginal fungus infections in mammalian species, such as humans,cats, dogs and the like. The suppository formulation will be easilyinserted into the vaginal cavity and will melt at body temperature soonafter insertion. Upon melting, the suppository turns into a gel/creamlike consistency, which will adheres to the vaginal membrane therebyproviding prolonged duration of effectiveness.

[0089] As mentioned above, a pharmaceutical or cosmetic composition inaccordance with the teachings of the present invention may include abiologically active substance. The following provides some examples.

[0090] Antiviral Agents:

[0091] The carrier or composition of the present invention is beneficialin the treatment of viral infections. For example, cold sores are causedby the herpes simplex Type 1 virus and are sometimes referred to asfacial herpes. Mollusca are small viral growths that appear singly or ingroups on the face, trunk, lower abdomen, pelvis, inner thighs or penis.Shingles (herpes zoster), which usually only occurs once in a lifetime,appears as a rash (clusters of blisters with a red base). It is causedby the same virus responsible for chickenpox. Warts are a common, benignskin tumor caused by viral infection. Eye viral infections, such asviral conjunctivitis is highly contagious and spreads by droplet,fomites, and hand-to-eye inoculation.

[0092] Viral infections are currently treated with various antiviralagents, as is summarized in Table 1 below: TABLE 1 Antiviral drugs DrugViruses Chemical Type Vidarabine Herpesviruses Nucleoside analogAcyclovir Herpes simplex (HSV) Nucleoside analog GancyclovirCytomegalovirus (CMV) Nucleoside analog Nucleoside-analog reversetranscriptase Retroviruses (HIV) Nucleoside analog inhibitors (NRTI):AZT (Zidovudine), ddI (Didanosine), ddC (Zalcitabine), d4T (Stavudine),3TC (Lamivudine) Non-nucleoside reverse transcriptase Retroviruses (HIV)Nucleoside analog inhibitors (NNRTI): Nevirapine, Delavirdine ProteaseInhibitors: Saquinavir, HIV Peptide analog Ritonavir, Indinavir,Nelfinavir Ribavirin Broad spectrum: HCV, Triazole carboxamic HSV,measles, mumps, Lassa fever Amantadine/Rimantadine Influenza A strainsTricyclic amine Interferons Hepatitis B and C Protein

[0093] It will be appreciated that the intrinsic antiviral effects ofthe solidifying agents, e.g., fatty alcohols and acids, provides asynergistic effect that will result in a higher therapeutic response.

[0094] Antiparasite Agents:

[0095] The biologically active substance contained in a composition ofthe present invention in a therapeutically effective amount may be anantiparasite agent, such as, but not limited to, hexachlorobenzene,carbamate, naturally occurring pyrethroids, permethrin, allethrin,malathion, piperonyl butoxide or mixtures of these drugs.

[0096] Antimicrobial Agents:

[0097] Antimicrobial agents, also referred to as germicidal agents,which may be used in compositions of the present invention includephenols, including cresols and resorcinols. Antibacterial compositionsaccording to the present invention may be used to treat infections ofthe skin. An example of a very common skin infection is acne, whichinvolve infestation of the sebaceous gland with p. acnes, as well asStaphylococus aurus or Pseudomonas. Various antibacterial agents havebeen utilized to treat acne, however, their efficacy is limited due totheir low penetration into the hydrophobic environment of the sebaceousgland. The composition of the present invention, being hydrophobic bynature would facilitate an enhanced rate of penetration. Examples ofuseful antiacne actives include the keratolytics such as salicylic acid(o-hydroxybenzoic acid), derivatives of salicylic acid such as5-octanoyl salicylic acid, and resorcinol; retinoids such as retinoicacid and its derivatives (e.g., cis and trans); sulfur-containing D andL amino acids and their derivatives and salts, particularly theirN-acetyl derivatives, a preferred example of which isN-acetyl-L-cysteine; lipoic acid; antibiotics and antimicrobials such asbenzoyl peroxide, octopirox, tetracycline, 2,4,4′-trichloro-2′-hydroxydiphenyl ether, 3,4,4′-trichlorobanilide, azelaic acid and itsderivatives, phenoxyethanol, phenoxypropanol, phenoxyisopropanol, ethylacetate, clindamycin and meclocycline; sebostats such as flavonoids; andbile salts such as scymnol sulfate and its derivatives, deoxycholate andcholate.

[0098] The intrinsic antibacterial and antiinflammatory effects of thesolidifying agents, i.e., fatty alcohols and acids, of the compositionof the present invention provide a combined synergetic effect thatresults in a better therapeutic response to treatment.

[0099] Eye infections are another preferred target for the compositionof the present invention. Conjuctivitis, involving bacteria such asStaphylococcus aureus, Streptococcus pneumoniae, and Haemophilusinfluenzae is generally treated with antibiotic ointments, e.g.,bacitracin 500 U/g or 0.3 percent ophthalmic ointment instilled into theaffected eye. Yet, ointment applied into the eye created a stickyfeeling and causes major disturbances to the patient. The composition ofthe present invention, which turns from semi-solid consistency intoliquid instantly after application, does not have that disadvantage andthus, treatment compliance is expected to improve. The same advantage isexpected when the composition of the present invention is topicallyapplied to mucosal membranes, the oral cavity, the vagina or the rectum.

[0100] Another example is parachlorometaxylenol, which is anantimicrobial agent and is suitable for use in the compositionsdescribed in the present invention.

[0101] Phenols, in concentrations of about 0.2, 1.0, and 1.3 percent byweight are bacteriostatic, bactericidal, and fungicidal, respectively.While it is not intended that the present invention be bound by anyparticular theory, it is believed that the germicidal action of phenolsat these concentrations is effected through protein denaturation. Thephenol-protein interaction is relatively weak, allowing the phenolmolecule to penetrate deeply into the tissue. Thus, phenol can penetraterelatively dense, intact keratinous matrices, such as the stratumcorneum or the nail plate. Several phenol derivatives are more potentthan phenol itself, and the most important among these are thehalogenated phenols and bis-phenols, the alkyl-substituted phenols andthe resorcinols.

[0102] Optionally, the present invention may provide a solution for bodyodors by including hydrophobic antibacterial compounds to help destroyand/or control the amount of bacteria present on the skin, which aids inbody odor control.

[0103] Hydrophobic antibacterials useful in the present inventioninclude triclosan, triclocarbon, eucalyptol, menthol, methylsalicylate,thymol, and mixtures thereof. Preferred are triclosan and triclocarbon.When included in the composition of the present invention, thehydrophobic antibacterials may be at a level of from about 0.1 percentto about 1.5 percent and preferably from about 0.1 percent to about 0.3percent, by weight of the composition.

[0104] Antifungal Agents:

[0105] Fungal infections are another object of treatment using thecompositions of the present invention. Superficial fungal infection ofthe skin is one of the commonest skin disease seen in general practice.Dermatophytosis is probably the most common superficial fungal infectionof the skin. It is caused by a group of fungi, which are capable ofmetabolizing the keratin of human epidermis, nails or hair. There are 3genera of dermatophytes causing dermatophytosis i.e., microsporum,trichophyton and epidermophyton.

[0106] Candidiasis is an infection caused by the yeast like fungusCandida albicans or occasionally other species of Candida. Clinicalsyndromes of candidiasis include (a) oral candidiasis (oral thrush); (b)candidiasis of the skin and genital mucous membrane; and (c) candidaparonychia, which inflicts the nail.

[0107] The pharmaceutical composition of the present invention cancontain an antifungal drug, which is active against dermatophytes andcandida. The drug may include azoles, diazoles, triazoles, miconazole,fluconazole, ketoconazole, clotrimazole, itraconazole griseofulvin,ciclopirox, amorolfine, terbinafine, Amphotericin B, potassium iodide,flucytosine (5FC) and any combination thereof at a therapeuticallyeffective concentration. U.S. Pat. No. 4,352,808 discloses3-aralkyloxy-2,3-dihydro-2-(1H-imidazolylmethyl)benzo[b]thiophenecompounds having antifungal and antibacterial activity.

[0108] Steroidal Antiinflammatory Agents:

[0109] Suitable steroidal antiinflammatory agents usable in thecomposition of the present invention may include, although are notlimited to, corticosteroids such as hydrocortisone,hydroxyltriamcinolone alphamethyl dexamethasone,dexamethasone-phosphate, beclomethasone dipropionate, clobetasolvalerate, desonide, desoxymethasone, desoxycorticosterone acetate,dexamethasone, dichlorisone, diflorasone diacetate, diflucortolonevalerate, fluadrenolone, fluclarolone acetonide, fludrocortisone,flumethasone pivalate, fluosinolone acetonide, fluocinonide, flucortinebutylester, fluocortolone, fluprednidene (fluprednylidene)acetate,flurandrenolone, halcinonide, hydrocortisone acetate, hydrocortisonebutyrate, methylprednisolone, triamcinolone acetonide, cortisone,cortodoxone, flucetonide, fludrocortisone, difluorosone diacetate,fluradrenalone acetonide, medrysone, amc, amcinafide, betamethasone andthe balance of its esters, chlorprednisone, chlorprednisone acetate,clocortelone, clescinolone, dichlorisone, difluprednate, flucloronide,flunisolide, fluoromethalone, fluperolone, fluprednisolone,hydrocortisone valerate, hydrocortisone cyclopentylproprionate,hydrocortamate, meprednisone, paramethasone, prednisolone, prednisone,beclomethasone dipropionate, betamethasone dipropionate, triamcinolone,and mixtures thereof may be used. The preferred steroidalantiinflammatory for use in the present invention is hydrocortisone.

[0110] Table 2 below provides a summary of currently availablecorticosteroid agent. TABLE 2 List of steroidal antiinflammatory agentsfor topical application Potency Compound Formulation Very Clobetasolproprionate Cream or ointment 0.05 percent high Halobetasol proprionateCream or ointment 0.05 percent High Betamethasone diproprionate Cream orointment 0.05 percent Betamethasone valerate Ointment 0.1 percentFluocinolone acetonide Cream 0.02 percent Halcinonide Cream or ointment0.1 percent Medium Betamethasone valerate Cream 0.1 percent Fluocinoloneacetonide Cream or ointment 0.020 percent Hydrocortisone valerate Creamor ointment 0.2 percent Triamcinolone acetonide Cream, ointment, orlotion 0.1 percent or 0.020 percent Low Hydrocortisone Cream, ointment,or lotion 2.5 percent or 1.0 percent

[0111] Since all corticosteroid drugs are hydrophobic, the carrier ofthe present invention is most suitable as a vehicle to facilitate anenhanced rate of penetration and better topical distribution thereof.

[0112] Furthermore, the intrinsic antiviral, antibacterial andantiinflammatory effects of the solidifying agents, i.e., fatty alcoholsand acids, provide a combined synergetic effect that should result in abetter therapeutic response to treatment.

[0113] Psoriasis is a very common chronic inflammatory skin disease,which may be the target of treatment using a composition of the presentinvention. Psoriasis is marked by periodic flare-ups of sharply definedred patches covered by a silvery, flaky surface.

[0114] Corticosteroid ointments, greasy preparations containing smallamount of water, are commonly used for treating psoriasis. Their maindisadvantage is in their stickiness, which remains for long time aftertreatment is over. In this respect it should be noted that the presentinvention exemplifies the use of a hydrocortisone containing compositionthat was prepared according to the teachings of the present invention(see Example 1 below). The hydrocortisone preparation was compared to acommercial composition (Example 2) and was shown be highly efficient inthe treatment of psoriatic patients. Major reduction in the severity ofthe disease symptoms, i.e., disappearance of the silvery scales, andreduction of the oedema, erythema and pruritus were observed. Moreoverthe patients reported that unlike the ointments which are currentlyavailable in the market (see Table 2 above), the composition of thepresent invention was well distributed and absorbed into the skin,without leaving an undesirable greasiness and shiny appearance whichcharacterized the prior art formulations.

[0115] Examples of other inflammatory diseases or disorders, which canbe treated by the composition of the present invention, wherein the drugis a steroid are: seborrheic dermatitis of the face and trunk,seborrheic blepharitis, contact dermatitis, stasis dermatitis(gravitational eczema; varicose eczema), exfoliative dermatitis(erythroderma), lichen simplex chronicus, pemphigus, conjuctivitis anduveitis.

[0116] Topical antihistaminic preparations currently available include 1percent and 2 percent diphenhydramine (Benadryl® and Caladryl®), 5percent doxepin (Zonalon®) cream, phrilamine maleate, chlorpheniramineand tripelennamine, phenothiazines, promethazine hydrochloride(Phenergan®) and dimethindene maleate. These drugs, as well asadditional antihistamines can also be included in the composition of thepresent invention.

[0117] Additionally, so-called “natural” antiinflammatory agents areuseful in context of the present invention. For example, candelilla wax,alpha bisabolol, aloe vera, Manjistha (extracted from plants in thegenus Rubia, particularly Rubia cordifolia), and Guggal (extracted fromplants in the genus Commiphora, particularly Commiphora mukul, may beused as an active ingredient in the composition of the presentinvention.

[0118] Non-Steroidal Antiinflammatory Drugs (NSAIDs):

[0119] Another preferred embodiment of the present invention isadministration of non-steroidal antiinflammatory drugs (herein NSAIDs)using a composition of the present invention. NSAIDs have been usedextensively in recent years for treatment of chronic rheumatic orarthritic conditions and for management of pain. The compounds arebelieved to bring relief by inhibiting biosynthesis of prostaglandins ataffected joints or in other tissue areas. Salicylic acid, or aspirin,and ibuprofen are well-known examples of NSAIDs drugs. Patients usingNSAIDs drugs administered orally face an increased risk for pepticulcers and gastrointestinal blood loss resulting in anemia. Such adversereactions especially plague patients taking NSAIDs drugs over prolongedperiods. Administration of NSAIDs to using the carrier of the presentinvention will prevent gastrointestinal complications associated withthe oral administration of NSAIDs. Such compositions can be used forprolonged treatment of arthritis and other diseases or disorders treatedby NSAIDs drugs, while avoiding the gastrointestinal complicationsassociated with oral dose delivery. Application of NSAIDs drugs in atopical composition to the skin of a patient allows a predeterminedamount of the NSAIDs drug to be administered continuously to the patientand avoids undesirable effects present with a single or multipleadministrations of larger dosages. By maintaining a sustained dosagerate, the NSAIDs drug level in the patient's blood can be bettermaintained within the optimal therapeutic range

[0120] Examples of NSAIDs include the following categories: propionic toacid derivatives; acetic acid derivatives; fenamic acid derivatives;biphenylcarboxylic acid derivatives; and oxicams. All of these NSAIDsare fully described in the U.S. Pat. No. 4,985,459 to Sunshine et al.which is incorporated herein by reference. Examples of useful NSAIDsinclude acetyl salicylic acid, ibuprofen, naproxen, benoxaprofen,flurbiprofen, fenoprofen, fenbufen, ketoprofen, indoprofen, pirprofen,carprofen, oxaprozin, pranoprofen, mniroprofen, tioxaprofen, suprofen,alminoprofen, tiaprofenic acid, fluprofen and bucloxic acid.

[0121] Antioxidants/Radical Scavengers:

[0122] Suitable antioxidants/radical scavengers useful in context of thepresent invention include ascorbic acid (vitamin C) and its salts,tocopherol (vitamin E), and its derivatives such as tocopherol sorbate,other esters of tocopherol, butylated hydroxy benzoic acids and theirsalts, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid(commercially available under the trade name Trolox®), gallic acid andits alkyl esters, especially propyl gallate, uric acid and its salts andalkyl esters, sorbic acid and its salts, the ascorbyl esters of fattyacids, amines (e.g., N,N-diethylhydroxylamine, amino-guanidine),sulfhydryl compounds (e.g., glutathione), and dihydroxy fumaric acid andits salts may be used, as well as EDTA, BHT and the like.

[0123] Antibiotics:

[0124] Antibiotics which may be used in context of the composition ofthe present invention, include, but are not limited to, chloramphenicol,tetracyclines, synthetic and semi-synthesic penicillins, beta-lactames,quinolones, fluoroquinolnes, macrolide antibiotics, peptide antibiotics,cyclosporines, erytromycin and clinndamycin.

[0125] Topical Anesthetics:

[0126] Examples of topical anesthetic drugs useful in context of thecomposition of the present invention include benzocaine, lidocaine,bupivacaine, chlorprocaine, dibucaine, etidocaine, mepivacaine,tetracaine, dyclonine, hexylcaine, procaine, cocaine, ketamine,pramoxine, phenol, and pharmaceutically acceptable salts thereof.

[0127] Retinoi:

[0128] Another preferred group of drugs useful in context of thecomposition of the present invention include retinol, all trans retinoicacid and derivatives, isomers and analogs thereof, collectively termed“retinoids”. Compositions according to the present invention, whichcontain retinoids as the active ingredient can be used for the treatmentof acne, seborrea, various dermatoses, inflammation of the skin, mucosalmembranes, eye, vagina and the rectum, psoriasis and cancers, byapplication onto the affected area.

[0129] Other Drugs:

[0130] As is further detailed hereinunder, it is possible to provide thecomposition of the present invention onto a dermal patch to generate atransdermal delivery apparatus and applying such patch onto the skin inorder to attain effective superficial treatment or enhanced penetrationof a drug into the skin or through the skin.

[0131] Utilizing such a strategy, one can apply drugs which arecurrently administered systemically or that require transdermaldelivery, in the preferred therapeutic system of the present invention.The following provides some examples for such drugs.

[0132] A broad range of analgesics may be utilized including, withoutlimitation, morphine, codeine, heroine, methadone, thebaine, orpiarine,buprenorphine, morphinans, benzomorphans, acetaminophen, butorphanol,diflunisal, fenoprofen, fentanyl, fentanyl citrate, hydrocodone,aspirin, sodium salicylate, ibuprofen, oxymorphone, pentaxicine,naproxen, nalbuphine, mefenamic acid, meperidine and dihydroergotamine.

[0133] A typical narcotic antagonist is haloxone. Exemplary antitussiveagents include, without limitation, diphenhydramine, guaifenesin,hydromorphone, ephedrine, phenylpropanolamine, theophylline, codeine,noscapine, levopropoxyphene, carbetapentane, chlorpehndianol andbenzonatate.

[0134] Among the sedatives which may be utilized are, withoutlimitation, chloral hydrate, butabarbital, alprazolam, amobarbital,chlordiazepoxide, diazepam, mephobarbital, secobarbital,diphenhydramine, ethinamate, flurazepam, halazepam, haloperidol,prochlorperazine, oxazepam, and talbutal.

[0135] Examples of cardiac drugs are, without limitation, quinidine,propranolol, nifedipine, procaine, dobutamine, digitoxin, phenytoin,sodium nitroprusside, nitroglycerin, verapamil HCl, digoxin, nicardipineHCl, and isosorbide dinitrate.

[0136] Antiemetics are illustrated by, without limitation,thiethylperazine, metoclopramide, cyclizine, meclizine,prochlorperazine, doxylamine succinate, promethazine, triflupromazine,and hydroxyzine.

[0137] A typical dopamine receptor agonist is bromocriptine mesylate.Exemplary amino acid, peptide and protein hormones include, withoutlimitation, thyroxine, growth hormone (GH), interstitial cellstimulating hormone (ICSH), follicle-stimulating hormone (FSH),thyrotropic hormone (TSH), adrenocorticotropic hormone (ACTH),gonadotropin releasing hormone (GnRH) such as leuprolide acetate,vasopressin and their active degradation products Some products may havesufficiently high molecular weights that absorption through the stratumcorneum or mucous membranes may be difficult. Therefore, the inventionis applicable only to those hormones which have molecular weights andstereo configurations which will allow passage through the skin.

[0138] Female sex hormones which can be used include, withoutlimitations, estradiol, diethylstilbestrol, conjugated estrogens,estrone, norethindrone, medroxyprogesterone, progesterone, andnorgestrel.

[0139] Typical male sex hormones which may be utilized may berepresented by, without limitation, testosterone, methyltestosterone,and fluoxymesterone.

[0140] The above listed active permeants may, along with others notspecifically disclosed, be used separately or in combination accordingto the treatment regimen desired.

[0141] Cosmetic Agents:

[0142] The carrier according to the present invention can also be usedto prepare cosmetics for beauty purpose by the addition of skin careagents and perfumes.

[0143] Sun Screen Agents:

[0144] Also useful in context of the composition of the presentinvention are sun screening agents. A wide variety of sun screeningagents are described in U.S. Pat. No. 5,087,445, to Haffey et al. U.S.Pat. No. 5,073,372, to Turner et al., U.S. Pat. No. 5,073,371, to Turneret al. and Segarin, et al., at Chapter VIII, pages 189 et seq., ofCosmetics Science and Technology all of which are incorporated herein byreference in their entirety. Preferred among those sunscreens which areuseful in the composition of the instant invention are those selectedfrom the group consisting of 2-ethylhexyl p-methoxycinnamate, octylmethoxycinnamate, 1-p-aminobenzoate, p-aminobenzoic acid,2-phenylbenzimidazole-5-sulfonic acid, octocrylene, oxybenzone,homomenthyl salicylate, octyl salicylate,4,4′-methoxy-t-butyldibenzoylmethane, 4-isopropyl dibenzoylmethane,3-benzylidene camphor, 3-(4-methylbenzylidene) camphor, titaniumdioxide, zinc oxide, silica, iron oxide, and mixtures thereof. Stillother useful sunscreens are those disclosed in U.S. Pat. Nos. 4,937,370,to Sabatelli and 4,999,186, to Sabatelli et al.. These two laterreferences are incorporated by reference herein in their entirety. Thesun screening agents disclosed therein have, in a single molecule, twodistinct chromophore moieties which exhibit different ultra-violetradiation absorption spectra. One of the chromophore moieties absorbspredominantly in the UVB radiation range and the other absorbs stronglyin the UVA radiation range. These sun screening agents provide higherefficacy, broader UV absorption, lower skin penetration and longerlasting efficacy relative to conventional sunscreens. Especiallypreferred examples of these sunscreens include those selected from thegroup consisting of 4-N,N-(2-ethylhexyl)methylanminobenzoic acid esterof 2,4-hydroxybenzophenone, 4-N,N-(2-ethylhexyl)methylaminobenzoic acidester with 4-hydroxydibenzoylmethane,4-N,N-(2-ethylhexyl)methylaminobenzoic acid ester of2-hydroxy-4-(2-hydroxyethoxy)benzophenone,4-N,N-(2-ethylhexyl)-methylaminobenzoic acid ester of4-(2-hydroxyethoxy)dibenzoylmethane, and mixtures thereof. Generally,the sunscreens can comprise from about 0.5 percent to about 20 percentof the compositions useful herein. Exact amounts will vary dependingupon the sunscreen chosen and the desired Sun Protection Factor (SPF).SPF is a commonly used measure of photoprotection of a sunscreen againsterythema. See Federal Register, Vol. 43, No. 166, pp. 38206-38269, Aug.25, 1978.

[0145] Artificial Tanning Agents and Accelerators:

[0146] Examples of artificial tanning agents accelerators which can beused in context of the present invention include dihydroxyacetone,tyrosine, tyrosine esters such as ethyl tyrosinate, and phospho-DOPA.

[0147] Reducing Body Odors:

[0148] The body fluids includes eccrine sweat, apocrine sweat, sebum,build up of sensible moisture from transepidermal water loss, vaginaldischarge, urine, and mixtures thereof. The body odor are odors, whichare generated as a result of the natural functioning of a human body.Such odors include, but are not limited to odors produced bymicroorganisms of the human skin (i.e. bacterial decomposition of skinsecretions), urine, or vaginal discharge, and mixtures thereof. Thepresent invention is therefore relevant to a method of reducing bodyodor comprising the application of a perfume-free, odor-absorbingcomposition which includes the carrier of the present invention.

[0149] Antiwrinkle and Antiskin Atrophy Agents:

[0150] Examples of antiwrinkle and antiskin atrophy actives which can beused in context of the present invention include retinoic acid and itsderivatives (e.g., cis and trans); salicylic acid and derivativesthereof, sulfur-containing D and L amino acids and their derivatives andsalts, particularly the N-acetyl derivatives, a preferred example ofwhich is N-acetyl L-gsteine; thiols, e.g. ethane thiol; alpha-hydroxyacids, e.g. glycolic acid, and lactic acid; phytic acid, lipoic acid;lysophosphatidic acid, and skin peel agents (e.g., phenol and the like).

[0151] Excipients and Additional Agents:

[0152] The pharmaceutical or cosmetic composition of the presentinvention may further include a variety of pharmaceutical or cosmeticingredients, which are added in order to fine-tune the consistency ofthe formulation, protect the formulation components from degradation andoxidation and bestow their cosmetic acceptability. Such excipients, maybe selected from the group consisting of water, surfactants,emulsifiers, diglycerides, triglycerides, stabilizing agents,antioxidants, glycerol, ethanol, propanol, isopropanol, butanol,polymeric gelling agents, flavoring, colorant and odorant agents andother formulation components, used in the art of pharmaceutical andcosmetic formulary.

[0153] Additional active and inactive ingredients may also include,without limitation, local analgesics such as benzocaine, menthol, andthe like (wherein menthol is also capable of providing a soothing,cooling sensation), as well emollients, antihistamines, fragrances,thickeners and preservatives other than those already listed.

[0154] Emollients:

[0155] The compositions of the present invention can also include anemollient. Emollient is used to smooth the surface of the skin. Examplesof suitable emollients include, but are not limited to, volatile andnon-volatile silicone oils (e.g., dimethicone, cyclomethicone,dimethiconol, and the like), highly branched hydrocarbons, and mixturesthereof. Emollients useful in the instant invention are furtherdescribed in U.S. Pat. No. 4,919,934, to Deckner et al., which isincorporated herein by reference in its entirety. The emollients cantypically comprise in total from about 0.1 percent to about 25 percent,more preferably from about 0.5 percent to about 10 percent, and mostpreferably from about 0.5 percent to about 5 percent by weight of thecomposition.

[0156] A variety of additional ingredients can be incorporated into thecomposition of the present invention. Non-limiting examples of theseadditional ingredients include vitamins and derivatives thereof (e.g.tocopherol, panthenol, and the like); other thickening agents (e.g.,polyacrylamide and C₁₃-C₁₄ isoparaffin and laureth-7, available asSepigel 305 from Seppic Corp., Fairfield, N.J.; and branchedpolysaccharides such as scleroglucan available under the tradenameClearogel® CS 11 from Michel Mercier Products Inc., Mountainside, N.J.);saturated and/or unsaturated alkyl alpha hydroxy acids; resins; gums(e.g. guar gum, xanthan gum and the like); waxes (both naturallyoccurring and synthetic); polymers for aiding the film-formingproperties and substantivity of the composition (such as a copolymer ofeicosene and vinyl pyrrolidone, an example of which is available fromGAF Chemical Corporation as Ganex V-220®); abrasive scrub particles forcleansing and exfoliating the skin, e.g., ACuscrub® Mild Abrasives(e.g., ACuscrub® 30, 31, 32, 40, 41, 42, 43, 44, 50, 51, and 52)available from Allied Signal, Inc., Morristown, N.J.; and 3M Brand PMUCapsules microecapsulated mineral oil available from 3M Corporation, St.Paul, Minn.!; preservatives for maintaining the antimicrobial integrityof the compositions; skin penetration aids such as DMSO,1-dodecylazacycloheptan-2-one (available as Azone® from the Upjohn Co.)and the like; skin bleaching (or lightening) agents including but notlimited to hydroquinone, kojic acid and sodium metabisulfite; chelatorsand sequestrants; and aesthetic components such as fragrances, pigments,colorings, essential oils, skin sensates, astringents, skin soothingagents, skin healing agents and the like, nonlimiting examples of theseaesthetic components include panthenol and derivatives (e.g. ethylpanthenol), aloe vera, pantothenic acid and its derivatives, clove oil,menthol, camphor, eucalyptus oil, eugenol, menthyl lactate, witch hazeldistillate, allantoin, bisabalol, dipotassium glycyrrhizinate and thelike.

[0157] The carrier system may also comprise, when desired, a suitablegelling agent including, but not limited to, cellulose esters such ashydroxypropyl cellulose (Klucel®), hydroxyethyl cellulose (Natrosol®),polyvinylpyrrolidone (Povidone®), carboxyvinyl polymer (HIVIS 105®) andthe like that may be provided in any amount necessary to thicken thecomposition to a desired gel consistency. When formulated as a gel, thebase composition exhibits favorable spreadability characteristics. Inaddition, it remains visible on the skin surface longer, therebyinstilling in the user the impression that the vehicle is morecompletely delivering its active ingredient(s).

[0158] In addition to the aforementioned ingredients, it should also benoted that the following ingredients may also be included in theinventive composition, as desired: coloring agents, fragrances,conditioners, moisturizers, surfactants, antioxidants, preservatives,etc.

[0159] Preferred ingredients are saturated and/or unsaturated alkylalpha hydroxy acids, at a level of from about 0.05 percent to about 5percent by weight of the composition, such as lactic acid, lactate salts(e.g., ammonium and quaternary alyl ammonium), glycolic acid, glycolatesalts (e.g., ammonium and quaternary allyl ammonium), and fruit acids. Adiscussion of alpha hydroxy acids is disclosed in Walter P. Smith,Hydroxy Acids and Skin Aging, Soap/Cosmetics/Chemical Specialties. pp.54-59, (September 1993), which is herein incorporated by reference inits entirety.

[0160] Preservatives:

[0161] Antimicrobial preservatives useful in the present inventioninclude biocidal and biostatic compounds (substances that killmicroorganisms and/or regulate the growth of microorganisms). Suitableantimicrobial preservatives have a solubility of 0.3 percent or greater.In addition, suitable preservatives are those which can come intocontact with skin without high irritation potential. Preservativessuitable for use in the present compositions are described in U.S. Pat.No. 5,534,165, to Pilosof et al.

[0162] It is preferable to use a broad spectrum preservative such as onethat is effective both on bacteria (both gram positive and gramnegative) and fungi. A limited spectrum preservative such as one that isonly effective on a single group of microorganisms, for example fungi,can be used in combination with a broad spectrum preservative or otherlimited spectrum preservatives with complimentary and/or supplementaryactivity. A mixture of broad spectrum preservatives can also be used.

[0163] Colorants and Dyes:

[0164] Colorants and dyes can be optionally added to the odor absorbingcompositions for visual appeal and performance impression. Whencolorants are used, care must be taken in the selection of choosing dyesthat will not color skin. Preferred colorants for use in the presentcompositions are highly water-soluble dyes, e.g., acid blue 3, acid blue104, acid green 1, acid green 25, acid yellow 3, acid yellow 73 sodiumsalt, D&C green No. 5, 6 & 8, D&C yellow No. 7, 8, 10 & 11, D&C violetNo. 2, FD&C blue No. 1 & 2, FD&C green No. 3, FD&C yellow No. 5 & 6, andmixtures thereof.

[0165] Other Optional Ingredients:

[0166] The composition of the present invention can optionally containadjunct odor-controlling materials, such as zinc salts, cationicpolymers, anionic polymers, carbonate salts, bicarbonate salts,zeolites, and activated carbon; chelating agents; colorants; and/orantiperspirants.

[0167] Optionally, the composition of the present invention can includezinc salts for added odor absorption and/or antimicrobial benefit forthe cyclodextrin solution. Zinc compounds have been used most often fortheir ability to ameliorate malodor, e.g., in mouth wash products, asdisclosed in U.S. Pat. No. 4,325,939 and U.S. Pat. No. 4,469,674 toShah, et al. Highly-ionized zinc salts, such as zinc chloride, providethe best source of zinc ions. The zinc salt, zinc phenolsulfonate, ispreferred for use in the skin composition of the present invention;although others may also fall within the scope of the present invention.However, care must be taken in selecting zinc salts, as well as theirlevels, since some may be irritants to the skin and they are notpreferred for use in the present invention.

[0168] Administration via Dermal Patch:

[0169] The compositions of the present invention may also be deliveredto the skin using conventional dermal-type patches or articles, whereinthe active ingredients composition is contained within a laminatedstructure, that serves as a drug delivery device to be affixed to theskin. In such a structure, the active ingredients composition iscontained in a layer, or “reservoir”, underlying an upper backing layer.The laminated structure may contain a single reservoir, or it maycontain multiple reservoirs. In one embodiment, the reservoir comprisesa polymeric matrix of a pharmaceutically acceptable contact adhesivematerial that serves to affix the system to the skin during activeingredients delivery. Examples of suitable skin contact adhesivematerials include, but are not limited to, polyethylenes, polysiloxanes,polyisobutylenes, polyacrylates, polyurethanes, and the like. Theparticular polymeric adhesive selected will depend on the particularactive ingredients, vehicle, etc., i.e., the adhesive must be compatiblewith all components of the active ingredients-containing composition.Alternatively, the active ingredients-containing reservoir and skincontact adhesive are present as separate and distinct layers, with theadhesive underlying the reservoir which, in this case, may be either apolymeric matrix as described above, or it may be a liquid or hydrogelreservoir, or may take some other form.

[0170] The backing layer in these laminates, which serves as the uppersurface of the device, functions as the primary structural element ofthe laminated structure and provides the device with much of itsflexibility. The material selected for the backing material should beselected so that it is substantially, impermeable to the activeingredients and to any other components of the activeingredients-containing composition, thus preventing loss of anycomponents through the upper surface of the device. The backing layermay be either occlusive or nonocclusive, depending on whether it isdesired that the skin become hydrated during active ingredientsdelivery. The backing is preferably made of a sheet or film of apreferably flexible elastomeric material. Examples of polymers that aresuitable for the backing layer include polyethylene, polypropylene, andpolyesters.

[0171] During storage and prior to use, the laminated structure includesa release liner. Immediately prior to use, this layer is removed fromthe device to expose the basal surface thereof, either the activeingredients reservoir or a separate contact adhesive layer, so that thesystem may be affixed to the skin. The release liner should be made froma active ingredients/vehicle impermeable material.

[0172] Such devices may be fabricated using conventional techniques,known in the art, for example by casting a fluid admixture of adhesive,active ingredients and vehicle onto the backing layer, followed bylamination of the release liner. Similarly, the adhesive mixture may becast onto the release liner, followed by lamination of the backinglayer. Alternatively, the active ingredients reservoir may be preparedin the absence of active ingredients or excipient, and then loaded by“soaking” in a active ingredients/vehicle mixture.

[0173] Therapeutic Effect and Dosage:

[0174] The therapeutic efficacy of the compositions described herein canbe determined by standard pharmaceutical procedures in experimentalanimal models or human beings. The data obtained from these studies canbe used in formulating a range of dosage for use in human (See e.g.,Fingl, et al., 1975, in “The Pharmacological Basis of Therapeutics”, Ch.1 p.1).

[0175] The effective concentration of the drug is calculated byprocedures known in the art that can be employed to determine theeffective local concentration. For example, corticosteroid inducedvasoconstriction in man may provide a preliminary useful hint to topicalantiinflammatory activity.

[0176] The amount of a composition to be administered will, of course,be dependent on the subject being treated, the severity of theaffliction, the manner of administration, the judgment of theprescribing physician, etc.

[0177] Short term studies over one or two weeks may not be the onlyrelevant investigation for the clinical comparison of the topical drugs.In practice these are sometimes applied over long periods of time andthe differences may be apparent only after months of treatment. For thisreason, depending on the novelty of the product and the indicationsclaimed, certain studies of efficacy as well as of safety will berequired.

[0178] Since the hydrophobic agent can be derived from a biologicalsource, it is necessary to assess the repeatability of the therapeuticeffect as well as the reproducibility, the specificity and the accuracyof the agent. This should be done by an analytical chemistry laboratorywhich is defined as GLP (Good Laboratory Practice).

[0179] Compositions of the present invention may, if desired, bepresented in a bottle or jar or other container approved by the FDA,which may contain one or more unit dosage forms containing the activeingredient. Compositions such as those described in the presentinvention may be particularly susceptible to microbial and othercontamination, and special measures need to be taken to prevent anycontamination. The pack or dispenser may also be accompanied by a noticeassociated with the container in a form prescribed by a governmentalagency regulating the manufacture, use or sale of pharmaceuticals, whichnotice is reflective of approval by the agency of the form of thecompositions or human or veterinary administration. Such notice, forexample, may be of labeling approved by the U.S. Food and DrugAdministration for prescription drugs or of an approved product insert.Compositions comprising a preparation of the invention formulated in acompatible pharmaceutical carrier may also be prepared, placed in anappropriate container, and labeled for treatment of an indicatedcondition. Suitable conditions indicated on the label may includetreatment for acne or for psoriasis and is the like.

[0180] The Gist and Advantages of the Present Invention Over the PriorArt:

[0181] The gist of the present invention is based on the strikingdiscovery that the addition of fatty alcohols to hydrophobic liquids,such as saturated, mono-unsaturated or poly-unsaturated oils, as well asmineral and silicone oils, may alter the physicochemical properties ofthe material, including the solidification thereof. This appears to beparticularly relevant when the fatty alcohol has a molecular weightgreater than 200 Da and at least one hydroxyl group in its chemicalstructure. The addition of a fatty alcohol to a liquid oil also givesrise to thixotropic properties (e.g., being semi-solid at rest andliquid upon application of shear forces thereto). This property enablesapplication of a thixotropic mixture as a semi-solid state to a bodysurface, which subsequently becomes substantially liquid and thereforemore spreadable and penetrable when rubbed onto the body surface. Thus,one of the most important properties of the carrier and composition ofthe present invention is that they are semi-solid at rest and that theyliquefy upon application of shear forces thereto. Semi-solid hydrophobicformulations are important not only for the pharmaceutical market butalso for cosmetic products, such as carriers of sunscreen compounds,oil-soluble plant extracts, materials for scrubbing purposes and otheractive and non-active cosmetic ingredients. Unlike aqueous liquids,which are rather easy to solidify due to their hydrogen bond formingability, oils are difficult to solidify. Several methods have beenproposed to increase the viscosity of oils. Various gelling agent, suchas inorganic complexing agents (U.S. Pat. No. 4,780,309), hydrocolloids(U.S. Pat. No. 4,576,645), polymers and copolymers (U.S. Pat. No.5,985,821; 5,925,707), polysaccharides (U.S. Pat. No. 5,961,998) havebeen previously described in the context of solidifying oils for use infood and cosmetics. The use of waxes, fatty alcohols, fatty acids and 12hydroxy stearic acid in solidifying waste oils, in order to facilitatethe removal of such oils have also been described (JP-A-112385/1979;JP-A-106298/1980). U.S. Pat. No. 5,817,322 teaches pharmaceuticalcompositions, comprising an oil and beeswax as a gelling agent, whichform a netted framework of the beeswax and form a film after applicationon a body surface.

[0182] However, the prior art fails to teach a carrier or compositionfor topical application which is semi-solid at rest and which liquefiesupon application of shear forces thereto.

EXAMPLES

[0183] Additional objects, advantages, and novel features of the presentinvention will become apparent to one ordinarily skilled in the art uponexamination of the following examples, which are not intended to belimiting. Additionally, the various embodiments and aspects of thepresent invention as delineated hereinabove and as claimed in the claimssection below finds experimental support in the following examples.

Example 1 Preparation of a Corticosteroid Composition

[0184] Stearyl alcohol (60 grams) was heated to 80° C. USP olive oil(940 grams) was heated to the same temperature. While at 80° C., thestearyl alcohol was added to the preheated olive oil. 20 grams glycerin,20 grams tri-stearin, 1 gram of an antioxidant mixture were added byagitation. 1 gram of betamethasone valerate was added and the mixturewas poured into containers (5 gram tubes) and was allowed to coolspontaneously. While the mixture cooled to ambient temperature itgradually turned into a semi-solid.

Example 2 Efficacy of the Corticosteroid Composition for the Treatmentof Psoriasis

[0185] In a preliminary experiment, five patients with psoriasis weretreated with the corticosteroid preparation described in Example 1,twice a day, for 10 days. In three out of five patients the psoriaticplaques and skin thickness were significantly reduced after 7-10 days oftreatment (FIG. 1). The forth patient had a moderate improvement andfifth showed only mild response to the treatment.

Example 3 A Double Blind Comparative Study Between the CorticosteroidComposition and a Conventional Ointment

[0186] Eight subjects were requested to apply 1 gram of thecorticosteroid composition described in Example 1 on one arm and 1 gramof commercial betamethasone valerate ointment, on the other arm. Thestudy was performed in a double blind manner. The subjects had todescribe their opinion about the ease of application, ease of spreading,spreadability and penetrability of each of the products and to givetheir scores on a scale of 0 to 3 (0=poor; 1=barely acceptable;2=acceptable and 3=excellent).

[0187] As can be clearly seen in Table 3 below, the corticosteroidcomposition of Example 1 obtained higher score in each of the studyparameters. TABLE 3 Comparison between the corticosteroid compositionand Betamethasone commercial ointment Corticosteroid CommercialComposition Betamethasone (Example 1) valerate ointment Parameters meanScore mean Score Ease of application 2.5 1.8 Ease of spreading 2.4 1.8Spreadability 2.8 1.6 Penetrability 2.4 2.0 Lack of stickiness 2.6 1.0Lack of greasiness 2.6 0.8 Lack of shiny look 1.9 1.4 Overall rating 2.61.6

[0188] Although the invention has been described in conjunction withspecific embodiments thereof, it is evident that many alternatives,modifications and variations will be apparent to those skilled in theart. Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims. All publications, patents and patentapplications mentioned in this specification are herein incorporated intheir entirety by reference into the specification, to the same extentas if each individual publication, patent or patent application wasspecifically and individually indicated to be incorporated herein byreference. In addition, citation or identification of any reference inthis application shall not be construed as an admission that suchreference is available as prior art to the present invention.

What is claimed is:
 1. A pharmaceutical or cosmetic carrier comprising,by weight, 1-25 percent of a solidifying agent and 75-99 percent of ahydrophobic solvent.
 2. The pharmaceutical or cosmetic carrier of claim1, wherein said solidifying agent is selected from the group consistingof at least one long chain fatty alcohol having at least 15 carbon atomsin its carbon backbone and at least one fatty acid, having at least 18carbon atoms in its carbon backbone.
 3. The pharmaceutical or cosmeticcarrier of claim 1, wherein said solidifying agent includes a substanceselected such that under ambient conditions, the carrier is semi-solidat rest and liquefies upon application of shear forces thereto.
 4. Thepharmaceutical or cosmetic carrier of claim 1, wherein said hydrophobicsolvent is selected from the group consisting of at least one marineanimal derived oil, at least one terrestrial animal derived oil, atleast one mineral oil, at least one silicone oil and at least oneplant-derived oil.
 5. The pharmaceutical or cosmetic carrier of claim 1,wherein said hydrophobic solvent includes an oil selected from the groupconsisting of olive oil, soybean oil, canola oil, rapeseed oil,cottonseed oil, coconut oil, palm oil, sesame oil, sunflower oil,safflower oil, rice bran oil, borage seed oil, syzigium aromaticum oil,hempseed oil, herring oil, cod-liver oil, salmon oil, corn oil, flaxseedoil, wheat germ oil, rape seed oil, evening primrose oil, rosehip oil,tea tree oil, melaleuca oil and jojova oil.
 6. The pharmaceutical orcosmetic carrier of claim 1, wherein said hydrophobic solvent includesan oil selected from the group consisting of omega-3 oil and omega-6oil.
 7. The pharmaceutical or cosmetic carrier of claim 2, wherein saidsolidifying agent has at least one alkyl group side chain in its carbonbackbone.
 8. The pharmaceutical or cosmetic carrier or composition ofclaim 2, wherein said carbon backbone of said fatty acid or said fattyalcohol has at least one hydroxyl group at position α and β.
 9. Thepharmaceutical or cosmetic carrier of claim 2, wherein said carbonbackbone of said fatty alcohol has at least one hydroxyl group atposition α and β.
 10. The pharmaceutical or cosmetic carrier of claim 2,wherein said carbon backbone of said fatty acid or said fatty alcoholhas at least one hydroxyl group at positions 8-14.
 11. Thepharmaceutical or cosmetic carrier of claim 2, wherein said solidifyingagent includes a 12-hydroxy fatty acid.
 12. The pharmaceutical orcosmetic carrier of claim 1, wherein at least one of said solidifyingagent and said hydrophobic solvent has a therapeutic or cosmeticbeneficial effect.
 13. A method of preparing a pharmaceutical orcosmetic carrier, the method comprising the steps of: (a) mixing ahydrophobic solvent and a solidifying agent at a temperature above amelting temperature of said solidifying agent so as to obtain a mixturecontaining 75-99 percent of said hydrophobic solvent by weight and 1-25percent of said solidifying agent by weight; and (b) cooling themixture.
 14. The method of claim 13, wherein prior to said step ofmixing, both said hydrophobic solvent and said solidifying agent arebrought to said temperature above said melting temperature of saidsolidifying agent.
 15. The method of claim 13, wherein said solidifyingagent is selected from the group consisting of at least one long chainfatty alcohol having at least 15 carbon atoms in its carbon backbone andat least one fatty acid, having at least 18 carbon atoms in its carbonbackbone.
 16. The method of claim 13, wherein said solidifying agentincludes a substance selected such that under ambient conditions, thecarrier is semi-solid at rest and liquefies upon application of shearforces thereto.
 17. The method of claim 13, wherein said hydrophobicsolvent is selected from the group consisting of at least one marineanimal derived oil, at least one terrestrial animal derived oil, atleast one mineral oil, at least one silicone oil and at least oneplant-derived oil.
 18. The method of claim 13, wherein said hydrophobicsolvent includes an oil selected from the group consisting of olive oil,soybean oil, canola oil, rapeseed oil, cottonseed oil, coconut oil, palmoil, sesame oil, sunflower oil, safflower oil, rice bran oil, borageseed oil, syzigium aromaticum oil, hempseed oil, herring oil, cod-liveroil, salmon oil, corn oil, flaxseed oil, wheat germ oil, rape seed oil,evening primrose oil, rosehip oil, tea tree oil, melaleuca oil andjojova oil.
 19. The method of claim 13, wherein said hydrophobic solventincludes an oil selected from the group consisting of omega-3 oil andomega-6 oil.
 20. The method of claim 15, wherein said solidifying agenthas at least one alkyl group side chain in its carbon backbone.
 21. Themethod of claim 15, wherein said carbon backbone of said fatty acid orsaid fatty alcohol has at least one hydroxyl group at position α and β.22. The method of claim 15, wherein said carbon backbone of said fattyalcohol has at least one hydroxyl group at position α and β.
 23. Themethod of claim 15, wherein said carbon backbone of said fatty acid orsaid fatty alcohol has at least one hydroxyl group at positions 8-14.24. The method of claim 15, wherein said solidifying agent includes a12-hydroxy fatty acid.
 25. The method of claim 13, wherein at least oneof said solidifying agent and said hydrophobic solvent has a therapeuticor cosmetic beneficial effect.
 26. A pharmaceutical or cosmeticcomposition comprising, by weight, 1-25 percent of a solidifying agentand 75-99 percent of a hydrophobic solvent, wherein at least one of saidsolidifying agent and said hydrophobic solvent has a therapeutic orcosmetic beneficial effect.
 27. The pharmaceutical or cosmeticcomposition of claim 26, wherein said solidifying agent is selected fromthe group consisting of at least one long chain fatty alcohol having atleast 15 carbon atoms in its carbon backbone and at least one fattyacid, having at least 18 carbon atoms in its carbon backbone.
 28. Thepharmaceutical or cosmetic composition of claim 26, wherein saidsolidifying agent includes a substance selected such that under ambientconditions, the carrier is semi-solid at rest and liquefies uponapplication of shear forces thereto.
 29. The pharmaceutical or cosmeticcomposition of claim 26, wherein said hydrophobic solvent is selectedfrom the group consisting of at least one marine animal derived oil, atleast one terrestrial animal derived oil, at least one mineral oil, atleast one silicone oil and at least one plant-derived oil.
 30. Thepharmaceutical or cosmetic composition of claim 26, wherein saidhydrophobic solvent includes an oil selected from the group consistingof olive oil, soybean oil, canola oil, rapeseed oil, cottonseed oil,coconut oil, palm oil, sesame oil, sunflower oil, safflower oil, ricebran oil, borage seed oil, syzigium aromaticum oil, hempseed oil,herring oil, cod-liver oil, salmon oil, corn oil, flaxseed oil, wheatgerm oil, rape seed oil, evening primrose oil, rosehip oil, tea treeoil, melaleuca oil and jojova oil.
 31. The pharmaceutical or cosmeticcomposition of claim 26, wherein said hydrophobic solvent includes anoil selected from the group consisting of omega-3 oil and omega-6 oil.32. The pharmaceutical or cosmetic composition of claim 26, wherein saidcarbon backbone of said fatty acid or said fatty alcohol has at leastone hydroxyl group at position α and β.
 33. The pharmaceutical orcosmetic composition of claim 26, wherein said carbon backbone of saidfatty alcohol has at least one hydroxyl group at position α and β. 34.The pharmaceutical or cosmetic composition of claim 26, wherein saidcarbon backbone of said fatty acid or said fatty alcohol has at leastone hydroxyl group at positions 8-14.
 35. The pharmaceutical or cosmeticcomposition of claim 26, wherein said solidifying agent includes a12-hydroxy fatty acid.
 36. The pharmaceutical or cosmetic composition ofclaim 26, wherein said carbon backbone of said fatty alcohol has atleast one hydroxyl group at position α and β.
 37. A pharmaceutical orcosmetic composition comprising: (a) a pharmaceutical or cosmeticcarrier containing, by weight, 1-25 percent of a solidifying agent and75-99 percent of a hydrophobic solvent; and (b) a therapeutically orcosmetically effective amount of a biologically active substance. 38.The pharmaceutical or cosmetic composition of claim 37, wherein saidsolidifying agent is selected from the group consisting of at least onelong chain fatty alcohol having at least 15 carbon atoms in its carbonbackbone and at least one fatty acid, having at least 18 carbon atoms inits carbon backbone.
 39. The pharmaceutical or cosmetic composition ofclaim 37, wherein said solidifying agent includes a substance selectedsuch that under ambient conditions, the carrier is semi-solid at restand liquefies upon application of shear forces thereto.
 40. Thepharmaceutical or cosmetic composition of claim 37, wherein saidhydrophobic solvent is selected from the group consisting of at leastone marine animal derived oil, at least one terrestrial animal derivedoil, at least one mineral oil, at least one silicone oil and at leastone plant-derived oil.
 41. The pharmaceutical or cosmetic composition ofclaim 38, wherein said hydrophobic solvent includes an oil selected fromthe group consisting of olive oil, soybean oil, canola oil, rapeseedoil, cottonseed oil, coconut oil, palm oil, sesame oil, sunflower oil,safflower oil, rice bran oil, borage seed oil, syzigium aromaticum oil,hempseed oil, herring oil, cod-liver oil, salmon oil, corn oil, flaxseedoil, wheat germ oil, rape seed oil, evening primrose oil, rosehip oil,tea tree oil, melaleuca oil and jojova oil.
 42. The pharmaceutical orcosmetic composition of claim 37, wherein said hydrophobic solventincludes an oil selected from the group consisting of omega-3 oil andomega-6 oil.
 43. The pharmaceutical or cosmetic composition of claim 37,wherein said solidifying agent has at least one alkyl group side chainin its carbon backbone.
 44. The pharmaceutical or cosmetic compositionof claim 38, wherein said carbon backbone of said fatty acid or saidfatty alcohol has at least one hydroxyl group at position α and β. 45.The pharmaceutical or cosmetic composition of claim 38, wherein saidcarbon backbone of said fatty alcohol has at least one hydroxyl group atposition α and β.
 46. The pharmaceutical or cosmetic composition claim38, wherein said carbon backbone of said fatty acid or said fattyalcohol has at least one hydroxyl group at positions 8-14.
 47. Thepharmaceutical or cosmetic composition of claim 38, wherein saidsolidifying agent includes a 12-hydroxy fatty acid.
 48. Thepharmaceutical or cosmetic composition of claim 37, wherein at least oneof said solidifying agent and said hydrophobic solvent has a therapeuticor cosmetic beneficial effect.
 49. The pharmaceutical or cosmeticcomposition of claim 37, wherein said biologically active substance isselected from the group of consisting of an antibiotic agent, a freeradical generating agent, an antifungal agent, an antiviral agent, anon-nucleoside reverse transcriptase inhibitor, a nucleoside-analogreverse transcriptase inhibitor, a protease inhibitor, a non-steroidalantiinflammatory drug, an immunosuppressant, an antihistamine agent, anantiinflammatory agent, a retinoid agent, a tar agent, an antipruriticsagent and a scabicide agent.
 50. The pharmaceutical or cosmeticcomposition of claim 49, wherein: (a) said antibiotic agent is selectedfrom the group consisting of chloramphenicol, tetracyclines, syntheticand semi-synthesic penicillins, beta-lactames, quinolones,fluoroquinolnes, macrolide antibiotics, peptide antibiotics,cyclosporines, erytromycin and clinndamycin; (b) said free radicalgenerating agent is benzoyl peroxide; (c) said antifungal agent isselected from the group consisting of azoles, diazoles, triazoles,miconazole, fluconazole, ketoconazole, clotrimazol, itraconazolegriseofulvin, ciclopirox, amorolfine, terbinafine, Amphotericin B andpotassium iodide; (d) said antiviral agent is selected from the groupconsisting of flucytosine (5FC), Vidarabine, acyclovir and Gancyclovir;(e) said nucleoside-analog reverse transcriptase inhibitor is selectedfrom the group consisting of Zidovudine, Stavudine and Lamivudine; (f)said non-nucleoside reverse transcriptase inhibitor is selected from thegroup consisting of Nevirapine and Delavirdine; (g) said proteaseinhibitor is selected from the group consisting of Saquinavir,Ritonavir, Indinavir, Nelfinavir, Ribavirin Amantadine, Rimantadine andInterferon; (h) said immunosuppressant is selected from the groupconsisting of Clobetasol proprionate, Halobetasol proprionate,Betamethasone diproprionate, Betamethasone valerate, Fluocinoloneacetonide, Halcinonide, Betamethasone valerate, Fluocinolone acetonide,Hydrocortisone valerate, Triamcinolone acetonide, Hydrocortisone andhexachlorobenzene; (i) said antiinflammatory agent is a vitamin B3 or aderivative thereof; (j) said retinoid agent is selected from the groupconsisting of isotretinoin, adapalene and tretinoin; (k) said tar agentis selected from the group consisting of coal tar and cade oil; (l) saidantihistamine agent is doxepine hydrochloride; (m) said antipruriticagent is crotampiton; and (n) said scabicide agent is selected from thegroup consisting of benzyl benzoate, malathion and crotamiton.
 51. Thepharmaceutical or cosmetic composition of claim 37, wherein saidbiologically active substance is effective in the treatment of a diseaseor disorder selected from the group consisting of psoriasis, acne,seborrhea, seborrheic dermatitis, alopecia and excessive hair growth,ichthyosis, wounds, burns, cuts, ulcers, psoriasis, seborrheicdermatitis of the face and trunk, seborrheic blepharitis, contactdermatitis, stasis dermatitis and exfoliative dermatitis.
 52. Thepharmaceutical or cosmetic composition of claim 51, wherein said statisdermatitis is selected from the group consisting of gravitationaleczema, varicose eczema and further wherein said exfoliative dermatitisis erythroderma.
 53. A method of preparing a pharmaceutical or cosmeticcomposition, the method comprising the steps of (a) mixing a hydrophobicsolvent and a solidifying agent at a temperature above a meltingtemperature of said solidifying agent so as to obtain a pharmaceuticalor cosmetic mixture containing 75-99 percent of said hydrophobic solventby weight and 1-25 percent of said solidifying agent by weight; and (b)further mixing into said carrier mixture a therapeutically orcosmetically effective amount of a biologically active substance. 54.The method of claim 53, wherein prior to said step of mixing, both saidhydrophobic solvent and said solidifying agent are brought to saidtemperature above said melting temperature of said solidifying agent.55. The method of claim 53, wherein said solidifying agent is selectedfrom the group consisting of at least one long chain fatty alcoholhaving at least 15 carbon atoms in its carbon backbone and at least onefatty acid, having at least 18 carbon atoms in its carbon backbone. 56.The method of claim 53, wherein said solidifying agent includes asubstance selected such that under ambient conditions, the carrier issemi-solid at rest and liquefies upon application of shear forcesthereto.
 57. The method of claim 53, wherein said hydrophobic solvent isselected from the group consisting of at least one marine animal derivedoil, at least one terrestrial animal derived oil, at least one mineraloil, at least one silicone oil and at least one plant-derived oil. 58.The method of claim 53, wherein said hydrophobic solvent includes an oilselected from the group consisting of olive oil, soybean oil, canolaoil, rapeseed oil, cottonseed oil, coconut oil, palm oil, sesame oil,sunflower oil, safflower oil, rice bran oil, borage seed oil, syzigiumaromaticum oil, hempseed oil, herring oil, cod-liver oil, salmon oil,corn oil, flaxseed oil, wheat germ oil, rape seed oil, evening primroseoil, rosehip oil, tea tree oil, melaleuca oil and jojova oil.
 59. Themethod of claim 53, wherein said hydrophobic solvent includes an oilselected from the group consisting of omega-3 oil and omega-6 oil. 60.The method of claim 53, wherein said solidifying agent has at least onealkyl group side chain in its carbon backbone.
 61. The method of claim55, wherein said carbon backbone of said fatty acid or said fattyalcohol has at least one hydroxyl group at position α and β.
 62. Themethod of claim 55, wherein said carbon backbone of said fatty alcoholhas at least one hydroxyl group at position α and β.
 63. The method ofclaim 55, wherein said carbon backbone of said fatty acid or said fattyalcohol has at least one hydroxyl group at positions 8-14.
 64. Themethod of claim 55, wherein said solidifying agent includes a 12-hydroxyfatty acid.
 65. The method of claim 53, wherein at least one of saidsolidifying agent and said hydrophobic solvent has a therapeutic orcosmetic beneficial effect.
 66. The method of claim 53, wherein saidbiologically active substance is selected from the group of consistingof an antibiotic agent, a free radical generating agent, an antifungalagent, an antiviral agent, a non-nucleoside reverse transcriptaseinhibitor, a nucleoside-analog reverse transcriptase inhibitor, aprotease inhibitor, a non-steroidal antiinflammatory drug, animmunosuppressant, an antihistamine agent, an antiinflammatory agent, aretinoid agent, a tar agent, an antipruritics agent and a scabicideagent.
 67. The method of claim 66, wherein: (a) said antibiotic agent isselected from the group consisting of chloramphenicol, tetracyclines,synthetic and semi-synthesic penicillins, beta-lactames, quinolones,fluoroquinolnes, macrolide antibiotics, peptide antibiotics,cyclosporines, erytromycin and clinndamycin; (b) said free radicalgenerating agent is benzoyl peroxide; (c) said antifungal agent isselected from the group consisting of azoles, diazoles, triazoles,miconazole, fluconazole, ketoconazole, clotrimazole, itraconazolegriseofulvin, ciclopirox, amorolfine, terbinafine, Amphotericin B andpotassium iodide; (d) said antiviral agent is selected from the groupconsisting of flucytosine (5FC), Vidarabine, acyclovir and Gancyclovir;(e) said nucleoside-analog reverse transcriptase inhibitor is selectedfrom the group consisting of Zidovudine, Stavudine and Lamivudine; (f)said non-nucleoside reverse transcriptase inhibitor is selected from thegroup consisting of Nevirapine and Delavirdine; (g) said proteaseinhibitor is selected from the group consisting of Saquinavir,Ritonavir, Indinavir, Nelfinavir, Ribavirin Amantadine, Rimantadine andInterferon; (h) said immunosuppressant is selected from the groupconsisting of Clobetasol proprionate, Halobetasol proprionate,Betamethasone diproprionate, Betamethasone valerate, Fluocinoloneacetonide, Halcinonide, Betamethasone valerate, Fluocinolone acetonide,Hydrocortisone valerate, Triamcinolone acetonide, Hydrocortisone andhexachlorobenzene; (i) said antiinflammatory agent is a vitamin B3 or aderivative thereof; (j) said retinoid agent is selected from the groupconsisting of isotretinoin, adapalene and tretinoin; (k) said tar agentis selected from the group consisting of coal tar and cade oil; (l) saidantihistamine agent is doxepine hydrochloride; (m) said antipruriticagent is crotampiton; and (n) said scabicide agent is selected from thegroup consisting of benzyl benzoate, malathion and crotamiton.
 68. Themethod of claim 53, wherein said biologically active substance iseffective in the treatment of a disease or disorder selected from thegroup consisting of psoriasis, acne, seborrhea, seborrheic dermatitis,alopecia and excessive hair growth, ichthyosis, wounds, burns, cuts,ulcers, psoriasis, seborrheic dermatitis of the face and trunk,seborrheic blepharitis, contact dermatitis, stasis dermatitis andexfoliative dermatitis.
 69. The method of claim 68, wherein said statisdermatitis is selected from the group consisting of gravitationaleczema, varicose eczema and further wherein said exfoliative dermatitisis erythroderma.
 70. A method of treating a disease or disorder of askin or a mucosal membrane comprising the step of topicallyadministrating to said skin or said mucosal membrane a pharmaceutical orcosmetic composition containing, by weight, 1-25 percent of asolidifying agent and 75-99 percent of a hydrophobic solvent, wherein atleast one of said solidifying agent and said hydrophobic solvent has atherapeutic or cosmetic beneficial effect.
 71. The method of claim 70,wherein said disease or disorder is selected from the group consistingof psoriasis, acne, seborrhea, seborrheic dermatitis, alopecia andexcessive hair growth, ichthyosis, wounds, burns, cuts, ulcers,psoriasis, seborrheic dermatitis of the face and trunk, seborrheicblepharitis, contact dermatitis, stasis dermatitis and exfoliativedermatitis.
 72. The method of claim 71, wherein said statis dermatitisis selected from the group consisting of gravitational eczema, varicoseeczema and further wherein said exfoliative dermatitis is erythroderma.73. The method of claim 70, wherein said mucosal membrane is selectedfrom the group consisting of a mucosa of a nose, a mucosa of a mouth, amucosa of an eye, a mucosa of an ear, a mucosa of a vagina and mucosa ofa rectum.
 74. The method of claim 70, wherein said disease or disorderis an inflammation caused by an inflammatory agent selected from thegroup consisting of a bacterial inflammatory agent, a fungalinflammatory agent, a viral inflammatory agent, a parasitic inflammatoryagent, an autoimmune inflammatory agent, an allergic inflammatory agent,a hormonal inflammatory agent and a malignant inflammatory agent. 75.The method of claim 70, wherein said solidifying agent is selected fromthe group consisting of at least one long chain fatty alcohol having atleast 15 carbon atoms in its carbon backbone and at least one fattyacid, having at least 18 carbon atoms in its carbon backbone.
 76. Themethod of claim 70, wherein said solidifying agent includes a substanceselected such that under ambient conditions, the carrier is semi-solidat rest and liquefies upon application of shear forces thereto.
 77. Themethod of claim 70, wherein said hydrophobic solvent is selected fromthe group consisting of at least one marine animal derived oils, atleast one terrestrial animal derived oil, at least one mineral oils, atleast one silicone oil and at least one plant-derived oils.
 78. Themethod of claim 70, wherein said hydrophobic solvent includes an oilselected from the group consisting of olive oil, soybean oil, canolaoil, rapeseed oil, cottonseed oil, coconut oil, palm oil, sesame oil,sunflower oil, safflower oil, rice bran oil, borage seed oil, syzigiumaromaticum oil, hempseed oil, herring oil, cod-liver oil, salmon oil,corn oil, flaxseed oil, wheat germ oil, rape seed oil, evening primroseoil, rosehip oil, tea tree oil, melaleuca oil and jojova oil.
 79. Themethod of claim 70, wherein said hydrophobic solvent includes an oilselected from the group consisting of omega-3 oil and omega-6 oil. 80.The method of claim 70, wherein said solidifying agent has at least onealkyl group side chain in its carbon backbone.
 81. The method of claim80, wherein said carbon backbone of said fatty acid or said fattyalcohol has at least one hydroxyl group at position α and β.
 82. Themethod of claim 80, wherein said carbon backbone of said fatty alcoholhas at least one hydroxyl group at position α and β.
 83. The method ofclaim 80, wherein said carbon backbone of said fatty acid or said fattyalcohol has at least one hydroxyl group at positions 8-14.
 84. Themethod of claim 70, wherein said solidifying agent includes a 12-hydroxyfatty acid.
 85. A method of treating a disease or disorder of a skin ora mucosal membrane comprising the step of topically administratingthereto a pharmaceutical or cosmetic composition containing: (a) apharmaceutical or cosmetic carrier containing, by weight, 1-25 percentof a solidifying agent and 75-99 percent of a hydrophobic solvent; and(b) a therapeutically or cosmetically effective amount of a biologicallyactive substance.
 86. The method of claim 85, wherein said mucosalmembrane is selected from the group consisting of a mucosa of a nose, amucosa of a mouth, a mucosa of an eye, a mucosa of an ear, a mucosa of avagina and mucosa of a rectum.
 87. The method of claim 85, wherein saidsolidifying agent is selected from the group consisting of at least onelong chain fatty alcohol having at least 15 carbon atoms in its carbonbackbone and at least one fatty acid, having at least 18 carbon atoms inits carbon backbone.
 88. The method of claim 85, wherein saidsolidifying agent includes a substance selected such that under ambientconditions, the carrier is semi-solid at rest and liquefies uponapplication of shear forces thereto.
 89. The method of claim 85, whereinsaid hydrophobic solvent is selected from the group consisting of atleast one marine animal derived oils, at least one terrestrial animalderived oil, at least one mineral oil, at least one silicone oil and atleast one plant-derived oil.
 90. The method of claim 85, wherein saidhydrophobic solvent includes an oil selected from the group consistingof olive oil, soybean oil, canola oil, rapeseed oil, cottonseed oil,coconut oil, palm oil, sesame oil, sunflower oil, safflower oil, ricebran oil, borage seed oil, syzigium aromaticum oil, hempseed oil,herring oil, cod-liver oil, salmon oil, corn oil, flaxseed oil, wheatgerm oil, rape seed oil, evening primrose oil, rosehip oil, tea treeoil, melaleuca oil and jojova oil.
 91. The method of claim 85, whereinsaid hydrophobic solvent includes an oil selected from the groupconsisting of omega-3 oil and omega-6 oil.
 92. The method of claim 85,wherein said solidifying agent has at least one alkyl group side chainin its carbon backbone.
 93. The method of claim 87, wherein said carbonbackbone of said fatty acid or said fatty alcohol has at least onehydroxyl group at position α and β.
 94. The method of claim 87, whereinsaid carbon backbone of said fatty alcohol has at least one hydroxylgroup at position α and β.
 95. The method of claim 87, wherein saidcarbon backbone of said fatty acid or said fatty alcohol has at leastone hydroxyl group at positions 8-14.
 96. The method of claim 85,wherein said solidifying agent includes a 12-hydroxy fatty acid.
 97. Themethod of claim 85, wherein said disease or disorder is inflammationcaused by an inflammatory agent selected from the group consisting of abacterial inflammatory agent, a fungal inflammatory agent, a viralinflammatory agent, a parasitic inflammatory agent, an autoimmuneinflammatory agent, an allergic inflammatory agent, a hormonalinflammatory agent and a malignant inflammatory agent.
 98. The method ofclaim 85, wherein said biologically active substance is effective in thetreatment of a disease or disorder selected from the group consisting ofpsoriasis, acne, seborrhea, seborrheic dermatitis, alopecia andexcessive hair growth, ichthyosis, wounds, burns, cuts, ulcers,psoriasis, seborrheic dermatitis of the face and trunk, seborrheicblepharitis, contact dermatitis, stasis dermatitis and exfoliativedermatitis.
 99. The method of claim 98, wherein said statis dermatitisis selected from the group consisting of gravitational eczema, varicoseeczema and further wherein said exfoliative dermatitis is erythroderma.100. The method of claim 85, wherein said disease or disorder isselected from the group consisting of psoriasis, acne, seborrhea,seborrheic dermatitis, alopecia and excessive hair growth, ichthyosis,wounds, burns, cuts, ulcers, psoriasis, seborrheic dermatitis of theface and trunk, seborrheic blepharitis, contact dermatitis, stasisdermatitis and exfoliative dermatitis.
 101. The method of claim 100,wherein said statis dermatitis is selected from the group consisting ofgravitational eczema, varicose eczema and further wherein saidexfoliative dermatitis is erythroderma.
 102. The method of claim 85,wherein said biologically active substance is selected from the group ofconsisting of an antibiotic agent, a free radical generating agent, anantifungal agent, an antiviral agent, a non-nucleoside reversetranscriptase inhibitor, a nucleoside-analog reverse transcriptaseinhibitor, a nucleoside-analog reverse transcriptase inhibitor, aprotease inhibitor, a non-steroidal antiinflammatory drug, animmunosuppressant, an antihistamine agent, an antiinflammatory agent, aretinoid agent, a tar agent, an antipruritics agent and a scabicideagent.
 103. The method of claim 102, wherein: (a) said antibiotic agentis selected from the group consisting of chloramphenicol, tetracyclines,synthetic and semi-synthesic penicillins, beta-lactames, quinolones,fluoroquinolnes, macrolide antibiotics, peptide antibiotics,cyclosporines, erytromycin and clinndamycin; (b) said free radicalgenerating agent is benzoyl peroxide; (c) said antifungal agent isselected from the group consisting of azoles, diazoles, triazoles,miconazole, fluconazole, ketoconazole, clotrimazole, itraconazolegriseofulvin, ciclopirox, amorolfine, terbinafine, Amphotericin B andpotassium iodide; (d) said antiviral agent is selected from the groupconsisting of flucytosine (5FC), Vidarabine, acyclovir and Gancyclovir;(e) said nucleoside-analog reverse transcriptase inhibitor is selectedfrom the group consisting of Zidovudine, Stavudine and Lamivudine; (f)said non-nucleoside reverse transcriptase inhibitor is selected from thegroup consisting of Nevirapine and Delavirdine; (g) said proteaseinhibitor is selected from the group consisting of Saquinavir,Ritonavir, Indinavir, Nelfinavir, Ribavirin Amantadine, Rimantadine andInterferon; (h) said immunosuppressant is selected from the groupconsisting of Clobetasol proprionate, Halobetasol proprionate,Betamethasone diproprionate, Betamethasone valerate, Fluocinoloneacetonide, Halcinonide, Betamethasone valerate, Fluocinolone acetonide,Hydrocortisone valerate, Triamcinolone acetonide, Hydrocortisone andhexachlorobenzene; (i) said antiinflammatory agent is a vitamin B3 or aderivative thereof; (j) said retinoid agent is selected from the groupconsisting of isotretinoin, adapalene and tretinoin; (k) said tar agentis selected from the group consisting of coal tar and cade oil; (l) saidantihistamine agent is doxepine hydrochloride; (m) said antipruriticagent is crotampiton; and (n) said scabicide agent is selected from thegroup consisting of benzyl benzoate, malathion and crotamiton.